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in  2010  witli  funding  from 

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Thermometer  Showing  Comparison  of  Fahrenheit 
AND  Centigrade  Scales 


QONVENIENT   COMPARISONS   OF   METRIC   AND   AvOXRDUPOIS   WEIGHTS 

I  kilogram   =       2.2046  pounds 
I  pound        =   453-6        grams 
I  ounce         =     28.3        grams 


THE 

ELEMENTS  OF  THE  SCIENCE 

OF 

NUTRITION 


BY 

GRAHAM  LUSK.  Ph.D.,  M.A..  F.R.S.  (Edin.) 

PROFESSOR     OF     PHYSIOLOGY     AT     THE    UNIVERSITY     AND     BELLEVUE     HOSPITAL 
MEDICAL  COLLEGE,   NEW  YORK  CITY 


ILLUSTRA  TED 


PHILADELPHIA  AND   LONDON 

W.    B.    SAUNDERS    COMPANY 

1906 


Copyright,  1906,  by  W.    B.   Saunders  Company 


PRESS    OF 
SAUNDERS    COMPANY 
PHILADELPHIA 


To 

Carl  von  Voit 

MASTER   AND    FRIEND 

FROM   WHOM   THE    AUTHOR   RECEIVED    THE    INSPIRATION 

OF    HIS    life's    WORK 

THIS   VOLUME  IS    DEDICATED. 


PREFACE. 

The  aim  of  the  present  book  is  to  review  the  scientific  sub- 
stratum upon  which  rests  the  knowledge  of  nutrition  both  in 
health  and  in  disease.  Throughout,  no  statement  has  been 
made  without  endeavoring  to  give  the  proof  that  it  is  true. 

The  widespread  interest  in  the  subject  of  nutrition  at  the 
present  time  leads  the  author  to  hope  that  this  book  may  prove 
of  value  to  the  student  of  dietetics  and  to  the  chnical  physician. 

Laboratory  methods  to  explain  the  inner  processes  in  dis- 
ease have  been  apphed  to  hospital  patients  for  twenty  years 
or  more  in  Germany,  but  in  the  United  States  httle  has 
been  done  in  this  regard.  If  such  investigations  are  in  any 
way  promoted  by  their  discussion  here  this  writing  will  not 
have  been  in  vain. 

On  a  previous  occasion  the  author  collected  the  more  im- 
portant information  concerning  the  Hfe  history  of  the  mineral 
constituents  of  the  body  for  the  American  Text  Book  of  Physi- 
ology, and  the  subject  has  been  allotted  Hmited  space  in  this 
volume. 

The  author  would  apologize  to  all  whose  claims  of  priority 
of  discovery  have  not  been  duly  recognized. 

He  wishes  to  express  his  great  obligation  to  a  former  pupil, 
Dr.  Margaret  B.  Wilson,  who  has  painstakingly  corrected 
the  manuscript. 

Graham  Lusk. 

Physiological  Laboratory,  Uxr'ersity  and 
Bellevue  Hospital  Medical  College, 
New  York,  October  i,   1906. 


13 


CONTENTS. 


CHAPTER  I.  Page. 

Introductory 17 

CHAPTER  n. 
The  Feces 45 

CHAPTER  III. 
Starvation 52 

CHAPTER  IV. 
The  Regulation  of  Temperature 78 

CHAPTER  V. 
The  Influence  of  Proteid  Food 98 

CHAPTER  VI. 
The  Specific  Dynamic  Action  of  the  Foodstuffs 133 

CHAPTER  VII. 

The  Influence  of  the  Ingestion  of  Fat  and  Carbohydrate 142 

CHAPTER  VIII. 

The  Influence  of  Mechanical  Work  on  Metabolism 160 

CHAPTER  IX. 
A  Normal  Diet 177 

CHAPTER  X. 

The  Food  Requirement  Dltiing  the  Period  of  Growth 193 

CHAPTER  XI. 

Metabolism  in  Anemia,  at  High  .A.ltitudes,  in  Myxedema  and  in 

EXOPHTH.A.LMIC  Goiter 212 

CHAPTER  XII. 
Metabolism  in  Di.a.betes  and  in  Phosphorus-Poisoning 225 

CHAPTER  XIII. 
Metabolism  in  Fever 249 

CHAPTER  XIV. 
PuRiN  Metabolism. — Gout 270 

CHAPTER  XV. 
Theories  of  Met.a.bolism  and  General  Review 288 

Appendix 299 

Index  of  Authors 309 

Index  of  Subjects 317 


IS 


THE   ELEMENTS  OF  THE  SCIENCE 
OF  NUTRITION. 


CHAPTER  I. 

INTRODUCTORY. 

The  earliest  scientific  observations  concerning  nutrition 
were  founded  upon  the  commonly  noted  fact  that  in  spite  of 
large  quantities  of  food  eaten,  a  normal  man  did  not  vary  greatly 
in  size  from  year  to  year.  It  was  understood  early  in  the  history 
of  physiology  that  the  weight  added  by  the  ingestion  of  food  and 
drink  was  lost  in  the  urine,  the  feces,  and  the  "insensible  per- 
spiration." The  "insensible  perspiration"  was  partly  in  evi- 
dence when  moisture  of  the  warm  breath  condensed  upon  a  cold 
plate.  By  it  was  meant  the  usually  invisible  exhalations  from 
the  body,  which  are  now  known  to  be  carbon  dioxid  and  water. 

Sanctorius^  made  many  experiments  upon  himself  and 
others  to  determine  the  amount  of  insensible  perspiration.  An 
old  cut  shows  him  sitting  in  a  chair  suspended  from  a  large  steel- 
yard. As  a  matter  of  routine  he  determined  his  own  weight 
previous  to  each  meal  and  then  weighted  the  steelyard  so  as  to 
counterbalance  the  additional  food  he  proposed  to  eat.  During 
the  meal  when  the  chair  dipped  he  ended  his  repast. 

In  Section  I,  Aphorism  II,  Sanctorius  gives  the  following 
curious  advice:  "If  a  physician  who  has  the  care  of  another's 
health,  is  acquainted  only  with  the  sensible  supplies  and  evacua- 
tions, and  knows  nothing  of  the  waste  that  is  daily  made  by  the 

^Sanctorius:  "De  medicina  statica  aphorisimi,"  Venice,  1614.  Trans- 
lation by  John  Quincy,  M.D.,  London,  1737. 

2  17  ' 


l8  SCIENCE   OF  NUTRITION. 

insensible  perspiration,  he  will  only  deceive  his  patient  and 
never  cure  him."  Aphorism  III  reads:  "He  only  who  knows 
how  much  and  when  the  body  does  more  or  less  insensibly  per- 
spire, will  be  able  to  discern  when  or  what  is  to  be  added  or 
taken  away  either  for  the  recovery  or  preservation  of  health." 

The  modern  era  of  the  science  of  nutrition  was  opened  by 
Lavoisier.  The  work  of  to-day  is  but  the  continuation  of  that 
done  a  century  and  more  ago.  Lavoisier  and  La  Place  made  ex- 
periments on  animal  heat  and  respiration.  The  great  German 
chemist  Liebig  derived  his  early  training  in  Paris,  residing  there 
in  1822.  Liebig's  conception  of  the  processes  of  nutrition  fired 
the  genius  of  Voit  to  the  painstaking  researches  which  laid  the 
foundation  of  his  Munich  school.  These  have  been  repeated 
and  extended  by  his  pupils,  of  whom  Rubner  is  chief,  and  by 
others  the  world  over.  Thus  the  knowledge  often  transmitted 
personally  from  the  master  to  the  pupil,  to  be  in  turn  elaborated, 
had  its  seed  in  the  intellect  of  Lavoisier.  It  was  he  who  first 
discovered  the  true  importance  of  oxygen  gas,  to  which  he  gave 
its  present  name.  He  declared  that  life  processes  were  those  of 
oxidation,  with  the  resulting  elimination  of  heat.  He  believed 
that  oxygen  was  the  cause  of  the  decomposition  of  a  fluid  brought 
to  the  lungs,  and  that  hydrogen  and  carbon  were  produced  in 
this  fluid  and  then  united  with  oxygen  to  form  water  and  carbon 
dioxid.  It  was  he  wlio  first  made  respiration  experiments  on 
man,  the  results  of  which  are  briefly  described  in  a  letter  to 
ISIonsieur  Terray,^  written  in  Paris  and  dated  November  19, 
1 790.  There  is  no  existing  record  of  the  apparatus  with  which 
Lavoisier  worked  and  early  obtained  accurate  results.  The 
more  important  conclusions  Lavoisier  sums  up  as  follows: 

1.  The  quantity  of  oxygen  absorbed  by  a  resting  man  at  a 

temperature  of  26°  C.  is  1200  pouces  de  France"^ 'howxXy. 

2.  The  quantity  of  oxygen  required  at  a  temperature  of  1 2°  C. 

rises  to  1400  pouces. 

'  Report  of  the  British  Association  for  the  Advancement  of  Science, 
Edinburgh,  1871,  p.  189. 

'  I   cubic  pouce — 0.0198  liters. 


INTRODUCTORY. 


19 


3.  During  the  digestion  of  food  the  quantity  of  oxygen 

amounts  to  from  1800  to  1900  pouces. 

4.  During  exercise  4000  pouces  and  over  may  be  the  quantity 

of  oxygen  absorbed. 

These  remarkable  results  are  in  strict  accord  with  the 
knowledge  of  our  own  day.  We  know  more  details,  but  the 
fundamental  fact  that  the  quantity  of  oxygen  absorbed  and  of 
carbon  dioxid  excreted  depends  primarily  on  (i)  food,  (2)  work, 
and  (3)  temperature,  was  estabhshed  by  Lavoisier  within  a  few 
years  after  his  discovery  that  oxygen  supported  combustion. 

It  was,  however,  quickly  noted  that  if  carbon  and  hydrogen 
burned  in  the  lungs,  the  greatest  heat  would  be  developed  there, 
a  result  not  in  accordance  with  observation.  It  was  then  sug- 
gested that  the  blood  dissolved  oxygen,  and  that  the  production 
of  carbon  dioxid  and  water  took  place  through  oxidation  within 
the  blood.  In  1837  Magnus  discovered  that  the  blood  did  hold 
large  quantities  of  oxygen  and  carbon  dioxid,  which  gave  apparent 
support  to  this  theory.  Ludwig  in  his  later  years  believed  that 
the  oxidation  took  place  in  the  blood. ^  Through  the  critical 
studies  of  Liebig,  which  were  pubHshed  in  1842,  it  was  seen  that 
it  was  not  carbon  and  hydrogen  which  burned  in  the  body,  but 
proteid,  carbohydrates,  and  fat.  Liebig's  original  theory  was 
that  while  oxygen  caused  the  combustion  of  fat  and  carbo- 
hydrates, the  breaking  down  of  proteid  was  caused  by  muscle 
work.  It  will  be  shown  later  that  oxygen  is  not  the  cause  of  the 
decomposition  of  materials  in  the  body,  but  that  this  decom- 
position proceeds  from  unkno\Mi  causes,  and  the  products 
involved  unite  with  oxygen.  These  chemical  changes  of  mate- 
rials under  the  influence  of  Hving  cells  is  known  as  metabolism. 
This  process  may  involve  two  factors,  cataholism,  or  the  reduction 
of  higher  chemical  compounds  into  lower,  and  anabolism,  or  the 
construction  of  higher  substances  from  lower  ones. 

Liebig  was  also  the  father  of  the  modern  methods  of  organic 
analysis,  and  with  him  began  the  great  accumulation  of  knowl- 
edge concerning  the  chemistry  of  the  carbon  compounds,  in- 

1  Verbal  statement  to  the  writer. 


20  SCIENCE   OF   NUTRITION. 

eluding  the  many  products  of  the  animal  economy.  These  dis- 
coveries gave  the  vi^orld  a  knowledge  of  the  constitution  of  foods, 
of  urine,  of  feces,  and  of  tissues,  which  was  not  possessed  by 
Lavoisier. 

Liebig  apphed  to  the  problems  of  biology  the  mental  wealth 
of  the  newer  chemistry  which  he  himself  was  creating.  He 
knew  that  proteid  contained  nitrogen,  and  in  1842  he  suggested 
that  the  nitrogen  in  the  urine  might  be  made  a  measure  of  the 
proteid  destruction  in  the  body.^  The  proof  that  such  was  the 
case  was  afforded  by  Carl  v.  Voit,^  who  established  the  fact  that 
an  animal  could  be  brought  into  what  he  called  nitrogenous 
equihbrium.  In  this  condition  the  nitrogen  of  the  proteid 
eaten  was  equal  to  the  nitrogen  ehminated  from  the  body  in  the 
urine  and  feces.  Thus  Voit  ^  fed  a  dog  for  fifty-eight  days  with 
29  kilograms  of  meat  containing  986.0  grams  of  nitrogen,  and 
found  982.8  grams  of  nitrogen  in  the  excreta  of  the  period.  The 
amount  of  N  in  the  urine  was  943.7  grams,  and  in  the  feces  39.1 
grams.  The  difference  between  the  amount  of  nitrogen  ingested 
and  that  recovered  in  the  excreta  was  only  three-tenths  of  one 
per  cent.  It  therefore  seemed  extremely  probable  that  the 
excretory  outlet  for  proteid  nitrogen  was  in  the  urine  and  in  the 
feces  and  that  other  sources  of  its  loss  were  normally  negligible. 
But  in  order  to  establish  the  fact  it  was  necessary  to  consider  the 
following  questions: 

Is  the  nitrogen  of  the  air  built  up  into  organic  compounds 
within  the  body  ?  Is  any  proteid  nitrogen  given  off  as  nitrogen 
gas?  As  ammonia  gas?  In  the  sweat?  How  much  is  lost 
through  the  growth  of  the  hair,  nails,  and  epidermis  ? 

Lavoisier  had  said  that  nitrogen  gas  had  nothing  to  do  with 
respiration.  Regnault  and  Reiset^  sometimes  found  that  ani- 
mals under  a  bell-jar  absorbed  nitrogen  gas  and  at  other  times 

'Liebig:  "Die  organische  Chemie  in  ihrer  Anwendung  auf  Physiologic 
und  Pathologie,"  1842. 

'Voit:  "Physiol.  Chem.  Untersuchungen,"  1857. 

'  Voit:  "Zeitschrift  fiir  Biologie,"  1866,  Bd.  ii,  p.  35. 

'' Regnault  and  Reiset:  "An.  de  chemie  et  phys.,"  Paris,  1849,  Sec.  3, 
Tome  xxvi. 


INTRODUCTORY.  21 

gave  it  off.  The  quantity  in  both  cases  was  extremely  small. 
Voit  explained  this  by  showing  that  the  blood  and  the  tissues 
always  contained  nitrogen  gas  dissolved  in  proportion  to  the 
partial  pressure  of  the  gas  in  the  atmosphere.  A  change  of  this 
partial  pressure  under  the  bell-jar  would  change  the  body's 
content  of  dissolved  nitrogen  and  explain  Regnault  and  Reiset's 
variations. 

The  experiments  of  Bachr  showed  that  a  rabbit  with  a 
tracheal  cannula  could  be  made  to  expire  for  six  hours  through 
Nessler's  reagent  without  the  indication  of  a  trace  of  ammonia 
in  the  breath.  This  has  also  been  shown  after  making  an 
Eck  fistula  in  a  dog,"  where  there  is  an  increase  in  the  amount 
of  ammonia  in  the  blood  and  in  the  urine.  The  lungs  are  not 
permeable  to  ammonia.^  The  ordinary  insensible  perspiration 
is  not  accompanied  by  any  appreciable  loss  of  nitrogenous 
excreta,  although  profuse  sweating  certainly  brings  out  some 
urea,  uric  acid,  and  other  nitrogen  extractives  normally  excreted 
in  the  urine.  The  recent  experiments  of  Benedict^  show  that 
the  cutaneous  excretions  of  a  resting  man  may  amount  to  0.071 
gram  nitrogen  per  day;  of  a  man  at  moderate  work  to  0.13 
gram  per  hour,  and  at  hard  work  to  0.22  gram  per  hour. 

Voit  ^  collected  the  hair  and  epidermis  from  a  dog  for  565 
days  and  found  an  average  daily  output  of  1.2  grams  with  0.18 
gram  of  nitrogen.  Moleschott®  cut  the  hair  and  nails  of  several 
men  once  a  month.  The  daily  outgrowth  of  hair  was  0.20  gram 
with  0.029  gram  of  nitrogen,  and  of  nail  substance  0.005  gram 
with  0.0007  gram  of  nitrogen.  The  waste  through  the  human 
epidermis  has  not  been  measured,  but  it  must  be  very  slight. 

The  above  sources  of  error  were  thus  shown  to  be  negligible. 

The  view  that  the  nitrogen  of  the  urine  and  feces  could  be 

*  Bachl:  "Zeitschrift  fiir  Biologic,"  1869,  Bd.  v,  p.  51. 

^Salaskin:  "Zeitschrift  fiir  physiologische  Chemic,"  1898,  Bd.  xxv,  p.  463. 

'Magnus:  "Archiv  fiir  ex.  Pathologic  und  Pharmakologie,"  1902,  Bd. 
xlviii,  p.  100. 

*  Benedict:  "Journal  of  Biological  Chemistry,"  1906,  vol.  i,  p.  263. 

*  Voit:  "Zeitschrift  fiir  Biologic,"  1866,  Bd.  ii,  p.  207. 

*  Moleschott:  "Untersuchungen  zur  Naturlehre,"  Bd.  xii,  p.  187. 


22  SCIENCE    OF    NUTRITION. 

made  a  measure  for  the  determination  of  proteid  metabolism 
was  thus  securely  established.  Urea,  the  principal  nitrogenous 
end-product  derived  from  proteid,  was  therefore  shown  to  be 
not  an  adventitious  product,  but  one  normally  proportional  to 
the  proteid  destruction.  It  was  known  that  meat  proteid  in 
general  contained  about  i6  per  cent,  of  nitrogen,  or  i  gram  of 
nitrogen  in  6.25  grams  of  proteid.  Therefore  for  every  gram  of 
nitrogen  found  in  the  excreta,  6.25  grams  of  proteid  have  been 
destroyed  in  the  body.  It  is  evident  that  if  proteid  nitrogen 
be  retained  in  the  body  a  new  construction  of  body  tissue  is 
indicated,  whereas  if  more  nitrogen  is  ehminated  than  is  in- 
gested with  the  food,  a  waste  of  body  tissue  must  take  place. 
The  discovery  of  the  method  of  calculating  the  proteid  metab- 
olism led  Voit  to  suggest  to  Pettenkofer  that  he  construct  an 
apparatus  with  which  the  total  carbon  excretion  might  be 
measured,  including  that  of  the  respiration  as  well  as  that  of  the 
urine  and  the  feces.  Voit  saw  that  with  these  data  it  would  be 
possible  to  determine  just  how  much  of  each  foodstuff  was 
actually  burned  in  the  human  body.  He  has  described  the 
delight  which  he  and  Pettenkofer  experienced  when  their  won- 
derful machine  began  to  tell  its  tale  of  the  hfe  processes.  The 
cost  of  the  apparatus,  which  was  considerable,  was  defrayed  by 
King  Maximilian  II  of  Bavaria. 

It  has  been  stated  that  the  form  of  Lavoisier's  respiration 
apparatus  is  unkno\Mi.  In  1850  Regnault  and  Reiset  *  pub- 
lished an  account  of  respiration  experiments  in  which  small 
animals  were  placed  under  a  bell-jar  containing  a  known  quan- 
tity of  oxygen.  The  air  was  kept  free  from  carbon  dioxid  by 
pumping  it  through  potassium  hydrate.  The  gaseous  exchange 
between  the  animal  and  its  environment  could  be  readily  ascer- 
tained, by  determining  the  amount  of  carbon  dioxid  given  ofiF 
and  the  amount  of  oxygen  absorbed.  No  attempt  was  made  to 
determine  from  what  materials  the  carbonic  acid  arose.  The 
method  of  Regnault  and  Reiset  placed  the  animals  in  a  confined 

'Regnault  and  Reiset:  "An.  d.  Chem.  und  Pharm.,"  1850,  Bd.  Ixxiii, 
pp.  92,  129,  257. 


INTRODUCTORY.  23 

space  where  poisonous  exhalations  other  than  carbon  dioxid 
could  collect,  and  where  the  atmosphere  became  saturated  with 
water.  Although  Regnault  and  Reiset  had  no  idea  of  the 
materials  which  were  oxidized  in  the  animals  with  which  they 
were  experimenting,  we  find  that  Bischoff  and  Voit  ^  tried  to  read 
such  interpretations  into  the  work  of  Regnault  and  Reiset.  Thus 
Bischoff  and  Voit  determined  the  quantity  of  nitrogen  in  the 
urine  of  a  starving  dog,  which  indicated  that  he  had  burned  in 
twenty-four  hours  218  grams  of  his  own  "flesh."  The  flesh 
was  calculated  from  the  nitrogen  elimination  on  the  basis  of 
the  knowledge  that  fresh  meat  contains  3.4  per  cent  of  nitrogen. 
Many  of  the  older  experiments  were  computed  on  this  basis. 
It  was  shown  that  the  218  grams  of  "flesh"  contained  40  grams 
of  carbon.  Bischoff  and  Voit  draw  attention  to  an  experiment 
of  Regnault  and  Reiset,  showing  that  a  meat-fed  dog  of  a  weight 
similar  to  the  above  gives  off  250  grams  of  carbon  and  absorbs 
900  grams  of  oxygen  in  the  respiration  of  twenty-four  hours. 
These  figures  indicated  to  Bischoff  and  Voit  that  the  extra 
carbon  elimination  was  due  to  the  combustion  of  fat,  and  they 
reached  the  conclusion  that  the  waste  of  the  body  in  starvation 
is  dependent  on  the  metaboHsm  of  proteid  and  fat.  Correct 
results,  however,  were  attainable  only  by  combining  the  two 
methods,  so  that  both  the  quantity  of  the  nitrogen  and  carbon 
of  the  urine  and  feces,  and  the  amount  of  carbon  dioxid  of  the 
respiration  during  the  same  period  of  time  could  be  ascertained. 
This  was  accompUshed  by  the  respiration  apparatus  of  Petten- 
kofer. 

The  problem  to  be  solved  by  Pettenkofer  included  the  main- 
tenance of  a  man  in  normal  surroundings.  A  small  room  was 
therefore  constructed  which  was  well  ventilated  by  a  current  of 
air.  This  air  entered  the  chamber  freely  through  an  opening 
in  connection  with  a  large  room  outside  and  was  aspirated  from 
a  second  opening  in  the  chamber,  through  a  large  gas-meter, 
where  its  volume  was  measured  (500,000  liters  per  day).     It 

^Bischoff  and  Voit:  "Die  Gesetze  der  Ernahrung  des  Fleischfressers," 
i860,  p.  43. 


24  SCIENCE    OF   NUTRITION. 

was  evidently  impracticable  to  determine  all  the  carbon  dioxid  in 
this  large  volume  of  air,  but  its  amount  was  calculated  from  the 
analysis  of  duplicate  samples  continually  withdrawn  from  the  air 
leaving  the  chamber  during  the  time  of  the  experiment.  Each 
sample,  as  it  was  pumped  out,  was  made  to  pass  over  ignited  pum- 
ice stone,  soaked  in  sulphuric  acid,  to  remove  the  water.  Next  it 
bubbled  through  baryta  water  to  remove  the  carbon  dioxid,  and 
then  passed  through  a  small  gas-meter,  where  the  volume  of  the 
sample  was  measured.  After  this  fashion  the  amount  of  carbon 
dioxid  and  water  coming  from  the  air  of  the  chamber  was 
determined  in  duplicate.  Other  duplicate  analyses  of  the  air 
taken  outside  the  ventilator,  just  before  it  entered  the  chamber, 
were  simultaneously  made  in  the  same  manner  as  were  the 
analyses  of  the  chamber  air  itself.  Knowing  the  quantity  of 
carbon  dioxid  and  water  entering  and  leaving  the  room,  it  was 
easy  to  calculate  how  much  was  derived  from,  the  man  living 
in  it  during  the  period  of  experimentation.  The  experi- 
menters failed  to  find  any  other  gaseous  exhalation  from  a  man, 
such  as  ammonia,  hydrogen,  or  methane,  which  could  vitiate 
their  results.  Control  experiments  were  made  by  burning  a 
candle  or  evaporating  a  known  weight  of  water  within  the  room. 
Analysis  showed  that  the  carbon  dioxid  and  water  so  produced 
were  measurable  within  one  per  cent,  of  error. 

As  an  illustration  of  the  practical  working  of  the  respiration 
apparatus  the  first  experiment  of  Pettenkofer  and  Voit,^  which 
gives  the  metaboHsm  in  a  starving  man,  will  be  described.  The 
man  was  allowed  a  small  quantity  of  Liebig's  extract  of  beef,  as 
the  experimenters  did  not  at  that  time  reaHze  the  very  slight 
discomfort  usually  entailed  by  total  abstinence  from  food.  As 
Liebig's  extract  has  no  nutritive  value,  its  effect  has  been  counted 
out  in  the  following  description. 

The  subject,  on  entering  the  living-room  of  the  apparatus, 
weighed  71.090  kilograms,  and  he  drank  during  the  day  1.0548 
liters  of  water,  making  a  total  body  weight  of  72.1448  kilograms. 
Twenty-four  hours  later  he  w^eighed  70.160  kilograms  and  his 

1  Pettenkofer  and  Voit:  "Zeitschrift  fiir  Biologic,"  1866,  Bd.  ii,  p.  478. 


INTRODUCTORY.  25 

excreta  had  amounted  to  0.7383  kilogram  carbon  dioxid,  0.8289 
kilogram  water'  in  the  respiration,  and  1.1975  kilograms  of 
urine.  The  final  body  weight  plus  all  the  excreta  amounted  to 
72.9247  kilograms.  A  total  body  weight  of  72.1448  kilograms 
was  converted  into  a  body  weight  plus  excreta  amounting  to 
72.9247.  The  difference  is  due  to  oxygen  absorbed.  The 
difference  of  0.7799  kilogram  represents  the  amount  of  oxygen 
needed  to  convert  the  body  substance  lost  into  the  excretory 
products  obtained.     The  tabular  statement  reads : 

MAN— STARVATION. 

Kg.  Kg. 

Weight  at  start .71.090  Weight  at  end 70.160 

Water  drunk 1.0548         Carbon  dioxid 0.7383 

Water  in   respiration 0.8289 

Oxygen  absorbed 0.7799         Urine i.i975 

72.9247  72.9247 

The  analysis  of  the  urine  showed  12.51  grams  of  nitrogen 
and  8.25  grams  of  carbon.  A  calculation  gives  the  amount  of 
carbon  in  the  respiration  as  201.3  grams.  If  we  neglect  the  feces 
as  being  too  small  in  starvation  to  influence  the  results,  we  find 
that  the  total  carbon  elimination  for  twenty-four  hours  was 
209.55  grams,  and  the  total  nitrogen  12.51.  In  the  Liebig 
extract  ingested  there  were  2.44  grams  of  carbon  and  1.18  grams 
of  nitrogen,  which  must  be  deducted  from  the  above  in  order  to 
obtain  the  strict  loss  of  carbon  and  nitrogen  from  the  body  during 
the  period  of  starvation.     These  values  are : 

C 207.11  grams. 

^ ^^-33 

These  two  figures  enabled  Pettenkofer  and  Voit  to  calculate 
what  substances  had  burned  in  the  body.  x\s  every  gram  of 
nitrogen  in  the  excreta  is  approximately  represented  by  the 
destruction  of  6.25  grams  of  meat  proteid,  the  amount  of  such 
proteid  destroyed  by  the  man  was  70.81  grams.  It  has  been 
found  that  for  every  gram  of  nitrogen  present  in  meat  proteid 
there  are  3.28  grams  of  carbon.  It  is  therefore  easy  to  estimate 
that  destruction  of  proteid  represented  by  11.33  grams  of  nitro- 


26  SCIENCE   OF  NUTRITION. 

gen  involved  the  elimination  of  37.16  grams  of  carbon.  Now, 
the  man  eliminated  207.11  grams  of  total  carbon,  from  which 
this  proteid  carbon  may  be  deducted,  leaving  as  residue  169.95 
grams,  which  must  have  originated  from  a  source  other  than 
proteid.  The  possible  sources  are  two  in  number — carbohy- 
drates and  fats.  In  starvation  no  carbohydrates  are  ingested 
and  their  supply  in  the  form  of  reserve  glycogen  is  usually 
counted  as  being  neghgible  in  such  experiments  as  these.  The 
only  other  source  from  which  the  169.95  grams  of  extra  carbon 
could  have  been  derived  is  fat,  and  as  fat  contains  76,52  per 
cent,  of  carbon,  a  destruction  of  222.1  grams  of  fat  may  be 
calculated.     This  fasting  man  therefore  destroyed: 

Proteid 70.81  grams. 

Fat _ 222.1         " 

That  such  metabolism  actually  did  take  place  was  further 
indicated  by  the  comparison  of  the  amount  of  oxygen  needed  for 
the  destruction  of  the  above  constituents,  and  the  amount  of 
oxygen  absorption  as  determined  by  the  experiment. 

From  the  constituents  of  the  proteid  and  fat  destroyed, 
Pettenkofer  and  Voit  deducted  the  constituents  of  the  urine, 
which  contains  part  of  the  C  and  H  belonging  to  proteid.  The 
balance  of  the  carbon  and  hydrogen  was  lit  for  oxidation  to 
carbon  dioxid  and  water.  Their  calculation  may  thus  be 
presented : 

Weight  i>f  Grams. 

C.                        H.  O. 

Composition  of  the  proteid  burned 37-i6                 5.8  17. i 

Composition  of  fat  burned 169.95                25.7  25.1 


Total  C,  H  and  O  metabolized 207.11  31.5  42.2 

Deduct  quantity  in  the  urine 8.2  2.0  7.6 


Balance  available  for  respiratory  COj  and  HjO . .    198.9  29.5  34.6 

Oxygen  required 530.4  235.7 

Total  O  required  for  the  formation  of  COj  and  HjO 766.  r 

Less  O  in  the  proteid  and  fat -  34.6 

Ox>'gen  actually  required 731-5 

Oxj'gen  absorption  as  determined 779-9 

Difference 48.4 


INTRODUCTORY.  27 

We  may  reach  the  same  result  by  using  the  most  modern 
figures  for  the  oxygen  requirement  in  the  metaboh'sm  of  the 
foodstuffs.  We  now  know  that  to  burn  loo  grams  of  meat 
proteid  requires  133.43  grams  of  oxygen,  and  to  burn  100  grams 
of  fat  requires  288.5  grams,  and  to  burn  100  grams  of  starch 
1 18.5  grams.     This  being  true,  there  are  required: 

Oxygen. 

For  70.81  grams  proteid 94-44  g- 

For  222.1      "       fat 639.55  g. 

Total  required    733-99  g- 

Ox}-gen  absorption  as  found 779-9    g- 

Difference 45-91 

Had  carbohydrates  burned,  less  oxygen  would  have  been 
needed,  since  carbohydrates  contain  a  larger  proportion  of 
oxygen  than  fats.  Had  the  extra  169.95  grams  of  carbon  been 
due  to  the  combustion  of  starch  (or  glycogen),  382  grams  would 
have  burned,  requiring  452.7  grams  of  oxygen  instead  of  639.5 
grams  for  fat.  Pettenkofer  and  Voit  found  in  the  amount  of 
oxygen  absorption  a  confirmation  of  their  belief  that  the  fasting 
organism  supports  itself  by  the  combustion  of  its  own  proteid 
and  fat. 

It  is  apparent  from  this  discussion  that  the  quantity  of 
oxygen  needed  in  metabolism  depends  upon  the  kind  of  material 
that  burns  in  the  organism,  and  also  that  the  relation  between 
the  amount  of  oxygen  absorbed  and  carbon  dioxid  excreted 
depends  on  the  same  factor.  Regnault  and  Reiset  frequently 
observed  that  this  latter  relationship  was  variable.  The  rela- 
tion of  the  volume  of  oxygen  inspired  to  the  volume  of  carbon 
dioxid  expired  is  called  the  respiratory  quotient.  When  carbo- 
hydrates burn,  the  R.  Q.  is  unity;  that  is,  for  every  hundred 
volumes  of  carbon  dioxid  excreted  a  hundred  volumes  of 
oxygen  are  absorbed.  When  proteid  burns  the  quotient 
y°|'  Q  -^  =^  7^  or  0.781,  and  when  fat  burns  the  quotient  is 
0.71.  Pettenkofer  and  Voit  calculated  that  the  respiratory  quo- 
tient in  their  fasting  man  was  0.69.  This  indicated  a  combus- 
tion of  fat  in  the  organism. 


28  SCIENCE    OF   NUTRITION. 

The  further  researches  of  Pettenkofer  and  Voit  were  founded 
on  the  principles  described  in  the  above  experiment  on  a  fasting 
man.  If  meat  and  fat  were  ingested,  the  carbon  and  nitrogen 
excreta  were  collected,  and  from  these  data  it  was  determined 
how  much  of  each  foodstuff  was  burned  and  whether  there  was 
a  storage  of  either  in  the  body  or  a  loss  of  either  from  the  body. 
If  a  mixed  diet  which  included  carbohydrates  were  given,  the 
carbon  dioxid  elimination  increased  and  the  oxygen  absorption 
was  such  as  indicated  the  combustion  of  carbohydrates.  It  was 
assumed  that  after  deducting  the  proteid  carbon  from  the  total 
carbon  eliminated,  the  balance  of  extra  carbon  was  derived 
from  the  destruction  of  the  carbohydrates  in  so  far  as  these  were 
ingested;  any  carbon  in  excess  of  this  was  attributed  to  fat 
combustion. 

Voit^  in  his  necrology  of  Pettenkofer  writes:  "Imagine  our 
sensations  as  the  picture  of  the  remarkable  processes  of  the 
metabolism  unrolled  before  our  eyes,  and  a  mass  of  new  facts 
became  known  to  us!  We  found  that  in  starvation  proteid  and 
fat  alone  were  burned,  that  during  work  more  fat  was  burned, 
and  that  less  fat  was  consumed  during  rest,  especially  during 
sleep;  that  the  carnivorous  dog  could  maintain  himself  exclu- 
sively on  a  proteid  diet,  and  if  to  such  a  proteid  diet  fat  were 
added,  the  fat  was  almost  entirely  deposited  in  the  body;  that 
carbohydrates,  on  the  contrary,  were  burned  no  matter  how 
much  was  given,  and  that  they,  like  the  fat  of  the  food,  protected 
the  body  from  fat  loss,  although  more  carbohydrates  than  fat  had 
to  be  given  to  effect  this  purpose ;  that  the  metabolism  in  the 
body  is  not  proportional  to  the  combustibility  of  the  substances 
outside  the  body,  but  that  proteid  which  bums  with  difficulty 
outside  metabolizes  with  the  greatest  ease,  then  carbohydrates, 
while  fat,  which  readily  burns  outside,  is  the  most  difficultly 
combustible  in  the  organism." 

Since  the  days  of  these  researches  repeated  experiments 
have  established  the  verity  of  the  conclusions  drawn.  It  is 
interesting  to  note  that  among  the  earliest  experiments  made 

'  Voit:  "Zeitschrift  fiir  Biologic,"  1901,  Bd.  xli,  p.  i. 


INTRODUCTORY.  29 

were  some  upon  patients  in  patliological  conditions,  one  suffer- 
ing from  leukemia,  the  other  from  diabetes. 

Besides  the  influence  of  foods  upon  metabolism,  the  changes 
brought  about  by  exercise,  temperature,  and  drugs  were  in- 
vestigated, not  only  by  the  Munich  school,  but  by  many  other 
workers.  Similar  investigations  are  actively  progressing  to- 
day. 

Among  the  important  conclusions  reached  by  Voit  was  that 
concerning  the  manner  of  the  metaboHsm.  It  has  been  stated 
that  Liebig  believed  that  fat  and  carbohydrates  were  destroyed 
by  oxygen,  while  proteid  metabolism  took  place  on  account  of 
muscle  work. 

Voit^  showed  that  muscle  work  did  not  increase  proteid 
metabolism  and  that  the  metabolism  was  not  proportional  to 
the  oxygen  supply.  The  oxygen  absorption  apparently  de- 
pended upon  what  metabolized  in  the  cells.  He  showed  that 
although  fat  burned  readily  in  the  air,  it  burned  only  with  great 
difficulty  in  the  body;  and  that  proteid  burned  with  comparative 
difficulty  in  the  air,  but  went  to  pieces  very  readily  in  the  body. 
Voit  believed  that  the  cause  of  metabolism  was  unkno^\'n,  that 
the  process  was  one  of  cleavage  of  the  food  molecules  into  simpler 
products,  which  could  then  unite  with  oxygen.  Yeast  cells,  for 
example,  convert  sugar  into  carbonic  acid  and  alcohol  without 
the  intervention  of  oxygen.  In  like  manner  the  first  products 
of  the  decomposition  of  fat,  sugar  and  proteid,  are  formed  in 
metaboHsm  through  unknown  causes.  Some  of  these  prelim- 
inary decomposition  substances  may  unite  with  oxygen  to  form 
carbon  dioxid  and  water,  others  may  be  converted  into  urea, 
while  others  under  given  circumstances  may  be  synthesized  to 
higher  compounds.  In  any  case  the  absorption  of  oxygen  does 
not  cause  metaboKsm,  but  rather  the  amount  of  the  metabolism 
determines  the  amount  of  oxvo;en  to  be  absorbed. 

The  statement  is  frequently  met  with  in  the  literature  of  the 
subject  that  such  and  such  a  disease  is  the  consequence  of  deficient 
oxidative  power  in  the  tissues.     For  example,  it  has  recently  been 

^  Voit:  "Zeitschrift  fiir  Biologic,"  1S69,  Bd.  v,  p.  169;  Bd.  ii,  p.  535.     . 


30  SCIENCE   OF   NUTRITION. 

stated  that  alcohol  decreases  the  oxidative  power  of  the  liver 
for  uric  acid/  Such  apparent  decrease  in  oxidative  power  may 
however  be  due  to  the  fact  that  the  normal  oxidizable  cleavage 
products  are  not  formed  and  therefore  no  oxidation  can  take 
place.  It  is  not  due  to  lack  of  oxygen  that  sugar  does  not  burn 
in  diabetes,  or  cystin  in  cystinuria.  There  is  the  normal  sup- 
ply of  oxygen  present,  but  the  cleavage  of  these  substances  into 
bodies  which  can  unite  with  oxygen  cannot  be  effected,  and 
hence  they  cannot  bum. 

Voit's  pupil,  Lossen,^  showed  that  the  carbon  dioxid  elimina- 
tion in  respiration  was  independent  of  the  ventilation  of  the  lungs 
except  in  so  far  as  forced  breathing  increased  the  muscular  work 
and  the  consequent  output  of  carbon  dioxid. 

Pfliiger,^  who  through  different  reasoning  came  to  the  same 
conclusion  as  Voit,  devised  an  experiment  in  which  a  rabbit 
breathed  quietly  through  a  cannula,  and  the  oxygen  absorption 
was  compared  with  that  of  the  same  animal  when  rapid  artificial 
ventilation  of  the  lungs  with  air  took  place,  producing  apnea  or 
hyperarteriahzation  of  the  blood.  There  was  no  difference, 
as  is  seen  from  the  following  table: 


Oxygen  Absorbed  in  C.C.  During  is  Minutes. 

Normal  respiration. 

Apnea. 

Series  I 

Series  II      

20I.66 
203.21 

203.88 
210.47 

From  these  experiments  it  is  made  sure  that  the  respiration 
does  not  cause  or  regulate  metabolism.  On  the  contrary,  the 
metabolism  regulates  the  respiration.  The  metabolism  of  the 
tissues,  through  its  oxygen  requirement  and  its  carbon  dioxid 
production,  changes  the  condition  of  the  blood  and  thereby 

'  Beebe,  S.  P.:  "American  Journal  of  Physiology,"  1904,  vol.  xii,  p.  36. 
'Lossen:  "Zeitschrift  fiir  Biologie,"  1866,  Bd.  ii,  p.  244;  and  1870,  Bd.  vi, 
p.  298. 

'Pfliiger:  "Archiv  fiir  die  ges.  Physiologie,"  1877,  Bd.  xiv,  p.  i. 


INTRODUCTORY.  3 1 

regulates  the  respiration.  These  distinctions  are  of  fundamental 
importance. 

Thus  far  the  history  of  the  principles  which  underhe  the 
exact  measurement  of  the  metabohsm  has  been  briefly  given. 
By  metabolism  is  meant  the  chemical  changes  of  materials  under 
the  influence  of  living  cells.  The  first  cause  of  these  chemical 
changes,  it  has  been  seen,  is  unknown,  but  their  results  lead  to 
motions  of  the  smallest  particles  of  protoplasm,  motions  whose 
totality  we  call  hfe.  Phenomena  of  hfe  are  phenomena  of 
motion,  due  to  liberation  of  energy  in  the  breaking  down  of 
molecules.  The  motions  are  principally  manifested  as  heat, 
mechanical  energy  and  electric  currents.  In  the  organism 
mechanical  energy  may  be  converted  into  heat,  as  appears  when 
the  work  of  the  heart  is  converted  into  heat  by  the  friction  of  the 
blood  upon  the  capillaries.  x\lso  the  current  of  electricity  de- 
veloped at  each  systole  of  the  heart,  or  in  any  other  active  tissue, 
is  resolved  into  heat.  Thus  heat  may  become  a  measure  of  the 
total  activity  of  the  body.  It  is  derived  from  the  total  metabo- 
lism and  must  be  dependent  on  it  and  be  a  measure  of  it.  Hence 
the  physical  activities  noted  in  life  are  the  results  of  chemical 
decompositions.  Metabolism  vivifies  the  energy  potential  in 
chemical  compounds. 

Lavoisier^  was  the  first  to  recognize  that  animal  heat  was 
derived  from  the  oxidation  of  the  body's  substance  and  to  com- 
pare animal  heat  to  that  produced  by  a  candle.  To  prove  this 
he  burned  a  known  quantity  of  carbon  in  an  ice-chamber  and 
noted  the  amount  of  ice  melted.  He  then  calculated  the  amount 
of  heat  produced  from  a  unit  of  carbon.  He  and  La  Place  put 
a  guinea-pig  in  an  ice-chamber  and  noted  the  amount  of  ice 
which  melted  during  ten  hours  and  calculated  the  heat  given 
oflF  from  the  animal.  They  then  determined  how  much  carbon 
dioxid  the  guinea-pig  gave  off.  The  animal  yielded  31.82 
calories  to  the  ice-chamber,  while  a  calculation  from  the  respira- 
tory analysis  showed  that   25.408   calories  could  have   been 

'  For  this  literature  see  Rubner:  "Zeitschrift  fiir  Biologic,"  1893,  Bd.  xxx, 
P-  73- 


32 


SCIENCE    OF    NUTRITION. 


derived  by  the  burning  of  enougli  carbon  to  yield  the  same 
amount  of  carbon  dioxid  as  was  eliminated  by  the  animal. 

Lavoisier  realized  several  of  the  errors  in  his  work.  For 
example,  the  calori metric  determination  on  the  animal  was 
made  at  a  different  temperature  from  that  of  the  respiratory 
experiment,  and  Lavoisier  knew  that  cold  would  raise  the 
carbon  dioxid  output.  Also  cold  reduced  the  heat  in  the  animal 
itself,  and,  further,  the  water  of  respiration  was  added  to  that 
of  the  melting  ice.  But  Lavoisier  concluded  that  the  source 
of  the  heat  lay  in  the  oxidation  of  the  body. 

Crawford,  in  England,  found  after  burning  wax  and  carbon, 
or  on  leaving  a  live  guinea-pig  in  his  water  calorimeter,  that  for 
every  hundred  ounces  of  oxygen  used  the  water  was  raised  the 
following  number  of  degrees  Fahrenheit : 

Wax 2.1 

Carbon i  .93 

Guinea-pig 1.73 

Crawford  concluded  that  the  heat  above  produced  was  due  to 
the  transformation  of  pure  air  into  fixed  air  (carbon  dioxid)  and 
water. 

The  method  of  Crawford  was  in  reality  one  of  considerable 
accuracy.  According  to  the  modern  computation  of  Zuntz  and 
Hageman^  the  following  are  the  values  of  heat  production 
where  one  liter  of  oxygen  is  used  to  burn  the  different  food- 
stuffs in  the  body: 

Calories. 

I  liter  of  oxvgen  used  in  the  metabolism  of  proteid  vields 4-691 

I   "     "       '"'  "        "  "  "  fat  '   "     4.686 

1    "     '■       "  "        "  "  "  starch        "     5.046 

This  table  shows  that  there  is  a  maximum  variation  of  only 
7  per  cent,  in  the  heat  value  of  a  unit  of  oxygen  to  the  body. 
Hence  the  quantity  of  oxygen  absorbed  may  be  utilized  as  an 
approximate  indicator  of  heat  production  (Fig.  9,  p.  259). 

In  1823  the  French  Academy  offered  a  prize  for  the  best 
essay  on  the  subject  of  animal  heat.  Depretz  and  Dulong 
competed  for  the  prize  and  it  was  awarded  to  the  former. 

'  Zuntz  and  Hageman:    "Stotfwechsel  des  Pferdes, "  1S98,  p.  245. 


INTRODUCTORY.  ^7, 

Depretz^  calculated  the  amount  of  heat  which  would  have 
been  Uberated  in  burning  the  carbon  and  hydrogen  of  the  metab- 
olism to  carbon  dioxid  and  water,  and  compared  this  with  the 
amount  of  heat  given  off  by  the  animal.  The  heat  as  calculated 
was  only  74  to  90  per  cent,  of  what  was  found.  So  Depretz 
concluded  that  although  the  respiration  was  the  principal  source 
of  animal  heat,  food,  the  motion  of  the  blood,  and  friction 
yielded  the  remainder.  Interpretation  along  the  lines  of  the  law 
of  the  conservation  of  energy  was  obviously  beyond  the  ideas  of 
the  time. 

Dulong's  -  experiments  also  led  to  the  same  conclusion,  that 
oxidation  was  insufficient  to  explain  the  cause  of  animal  heat, 
and  that  there  must  be  other  sources  of  it. 

In  1 85 1  R.  Mayer  laid  down  the  law  of  the  conservation  of 
energy,  and  Helmholtz  demonstrated  its  general  appHcabihty. 

Energy  cannot  arise  from  nothing,  nor  can  energy  disappear 
into  nothing.  Where  energy  is  active  it  must  have  been  else- 
where potential.  The  sum  total  of  energy  remains  constant  in 
the  universe,  but  energy  may  vary  in  kind.  The  kinds  include 
mechanical  energy,  heat,  electricity,  magnetism,  and  potential 
energy.  The  source  of  energy  on  the  earth  is  the  sun,  except- 
ing the  energy  of  the  tides,  which  is  due  principally  to  the 
moon.  The  sun  unevenly  warms  the  atmosphere,  producing 
winds  which  drive  ships,  and  windmills.  The  sun's  heat  lifts 
the  vapor  of  water  into  the  atmosphere,  producing  rain,  in 
consequence  of  .which  rivers  are  made  to  turn  machinery.  The 
sunlight  acts  upon  a  mixture  of  hydrogen  and  chlorin  gas,  caus- 
ing them  to  unite  with  a  loud  explosion,  and  the  sun  acts  upon 
the  green  leaf  of  the  plant,  causing  it  to  unite  carbon  dioxid  and 
water,  with  the  production  of  formic  aldehyde,  which  is  built  up 
into  sugar,  oxygen  being  given  off  in  the  process.  The  sun's 
energy  required  to  build  up  the  compound  becomes  latent  or 
potential  in  it.  Whenever  and  wherever  this  sugar  is  again  con- 
verted into  carbon  dioxid  and  water  by  oxidation,  exactly  the 

^  Depretz:  "  Annal.  de  chim.  et  de  phys.,"  1824. 
^Dulong:  Ibid.,  1841. 


34  SCIENCE   OF   NUTRITION. 

same  quantity  of  energy  taken  from  the  sun  and  made  potential  in 
the  sugar  is  set  free.  This  sugar  in  the  plant  may  be  further  con- 
verted into  starch,  cellulose,  fat,  and  possibly  into  proteid. 
Plants  furnish  wood  and  coal  as  fuel  for  the  steam-engine. 
They  also  furnish  the  basis  of  animal  food,  yielding  substances 
which  can  build  up  animal  tissues,  and  which  can  furnish  the 
energy  necessary  to  maintain  those  motions  in  the  cells  whose 
aggregate  is  called  life.  These  motions  appear  in  the  body 
as  heat,  mechanical  work,  and  electric  currents,  all  of  which 
may  be  measured  as  heat.  Is  this  heat  production  completely 
derived  from  the  metabohsm?  This  question  is  but  the  con- 
tinuation of  the  old  one  of  Lavoisier  in  the  light  of  newer 
science. 

Bischoff  and  Voit^  in  i860  still  calculated  the  heat  value  of 
the  metabohsm  from  the  heat  developed  in  burning  the  carbon 
and  hydrogen  elements  of  the  metabolism.  They  recognized, 
however,  that  this  was  a  false  method,  and  stated  that  they 
should  employ  the  calorific  value  of  fat,  starch,  and  proteid, 
less  the  urea,  since  they  recognized  that  urea  was  capable  of 
undergoing  combustion  with  liberation  of  heat. 

In  i860  Voit^  brought  a  Thomson  calorimeter  with  him  from 
London  to  Munich.  After  Frankland's  determination  of  the 
heat  value  of  the  various  foodstuffs  and  urea  Voit  ^  prepared  a 
table  in  1866  for  use  in  his  lectures  showing  that  the  metabolism 
of  the  fasting  man  experimented  on  by  Pettenkofcr  and  Voit 
indicated  the  production  of  2.25  million  small  calories,  while 
the  metabolism  on  a  medium  diet  was  2.40  million  calories. 

In  1873  Pettenkofer  and  Voit  *  calculated  that  100  grams 
of  fat  were  the  physiological  equivalent  of  175  grams  of 
starch.  Liebig  at  that  time  had  suggested  that  the  amount  of 
these  substances  which  could  be  burned  by  a  man  was  propor- 
tional to  the  oxygen  supply. 

'  Bischoff  and  Voit:  "Die  Gesetze  der  Ernahrung  des  Fleischfressers," 
i860,  p. 43. 

^Voit:  "Miinchener  medizinische  Wochenschrift,"  1902,  Bd.  xlix,  p.  233 

^  Voit:  Loc.  cit. 

*  Pettenkofer  and  Voit:  "Zeitschrift  fiir  Biologie,"  1873,  Bd.  ix,  p.  534. 


INTRODUCTORY.  35 

Voit,  not  content  with  his  results,  suggested  to  Schiirmann 
in  1878-79  that  he  carry  on  experiments  to  see  in  what  way 
carbohydrates  and  fat  were  interchangeable  in  nutrition.  Schiir- 
mann died  before  the  work  was  completed  and  the  investigation 
was  continued  by  Rubner.  The  isodynamic  law,  which  showed 
that  the  foodstuffs  replaced  each  other  in  accordance  with  their 
heat-producing  value,  was  the  result. 

After  Stohmann^  pubUshed  his  research  on  the  calorific 
value  of  foods,  urea,  etc.,  Voit  commenced  the  construction  of 
a  calorimeter  for  the  measurement  of  the  heat  eliminated  from 
the  body  of  a  man  whose  metabolism  was  simultaneously  de- 
termined. The  results  obtained  by  the  use  of  this  machine  have 
never  been  pubhshed. 

Rubner^  in  Voit's  laboratory  during  this  same  period  was 
making  a  series  of  valuable  calorimetric  determinations.  The 
heat  value  to  the  body  of  burning  starch  and  fat  were  obviously 
the  same  as  that  determined  in  the  calorimeter,  since  in  both 
cases  the  same  end-products,  carbon  dioxid  and  water,  resulted. 
The  heat  value  of  proteid  in  the  calorimeter  was  different  from 
its  fuel  value  to  the  body,  since  the  end-products  were  different 
in  the  two  cases.  When  proteid  burns  in  the  body,  the  products 
of  its  metabolism  are  lost  in  three  different  ways — through  the 
respiration,  urine,  and  feces.  The  last  two  contain  latent  heat 
lost  to  the  body,  which  must  be  deducted  from  the  heat  value 
of  proteid  determined  calorimetrically. 

The  custom  of  Stohmann  and  previous  authorities  had  been 
to  deduct  the  heat  value  of  urea  from  the  heat  value  of  proteid, 
in  order  to  obtain  the  actual  physiological  or  fuel  value  of  proteid 
for  the  organism.  But  in  the  earhest  experiments  of  Petten- 
kofer  and  Voit^  it  was  recognized  that  in  starvation  urine,  and 
in  urines  after  the  ingestion  of  meat,  there  was  a  much  larger 
output  of  carbon  in  the  urine  than  corresponded  to  the  quantity 

^  Stohmann:  "Journal  fur  praktische  Chemie, "  18S5,  Bd.  xxxi,  p.  273,  and 
earlier  papers. 

^  Rubner:  "Zeitschrift  fiir  Biologie,"  18S5,  Bd.  xxi,  pp.  250  and  337. 

^  Pettenkofer  and  Voit:  Ibid.,  1866,  Bd.  ii,  p.  471. 


36 


SCIENCE    OF   NUTRITION. 


of  urea  present.  The  ratio  of  nitrogen  to  carbon  was  nearly 
constant  in  the  urine  when  the  conditions  of  feeding  were  similar. 
If  urea  alone  were  present,  Rubner  estimated  there  would  be 
0.429  grams  of  C  to  i  of  N  or  an  N :  C=  i :  0.429.  In  starvation 
the  urine  contains  extractive  nitrogen  (creatinin,  uric  acid,  etc., 
having  relatively  more  carbon  than  urea)  which  has  been  de- 
rived from  the  breaking  down  of  tissue  proteid,  and  the  ratio  is 
N :  C=  1 : 0.728.  When  meat  was  ingested  the  fact  that  the  food 
contained  these  extractives  made  the  N:C  ratio  0.610.  And 
even  after  six  days'  ingestion  of  meat  washed  free  from  extractives 
the  urine  of  the  seventh  and  eighth  days  still  showed  an  elimina- 
tion of  carbon  other  than  that  due  to  urea,  as  was  indicated 
by  the  ratio  0.532.  Therefore,  from  the  metabolism  following 
the  ingestion  of  the  proteids  of  washed  meat  small  amounts 
of  carbon  compounds  other  than  urea  are  eliminated  in  the 
urine. 

Rubner  saw  that  it  was  the  heat  value  of  the  urinary  con- 
stituents themselves  which  had  to  be  subtracted  from  the  heat 
value  of  proteid  if  the  fuel  value  of  proteid  to  the  body  was  to  be 
determined. 

The  following  table  shows  Rubner's  results  after  burning 
the  dry  urine : 


CALORIC  VALUE  OF  URINE. 


Material  Burned. 

N:  C. 

Calories 
FROM  I  Gram. 

Calorific  Value 
OF  I  Gram  N. 

Urea 

0.429 

0-532 
0.610 
0.728 

2-523 
2.706 

2-954 
3.101 

5-41 

5-69 
7.46 

8.49 

Urine  after  feeding  proteid 

Urine  after  feeding  meat 

Urine  in  starvation 

It  was  not  alone  necessary  to  know  the  heat  value  of  the 
urine  excreted,  but  also  that  of  the  feces.  Rubner  found  that 
after  giving  100  parts  of  dry  muscle  containing  5.5  grams  of 
ash  there  was  an  elimination  of  38.2  grams  of  the  organic 
part  in  the  urine  and  2.7  grams  in  the  feces.  The  following 
table  represents  this  division  of  material  in  the  excreta : 


INTRODUCTORY.  37 

C.              H.  N.  O. 

Composition  of  100  parts  dr>' muscle 50.5  7.6  15.4  20.97 

Urine  contains  38.2  parts 9.63  2.52  i5-i6  10.9 

Feces  contain  2.7  parts 1.67  0.25  0.24  0.54 

Excreted  in  urine  and  feces    ii-3o         2.77         15-40         ii-44 

Balance  for  respiration 39.2  4.8  9.53 

Rubner  determined  the  amount  of  heat  produced  from  i 
gram  of  ash-free  feces  after  meat  ingestion  and  found  it  to  be 
6.127  calories,  while  i  gram  of  ash-free  feces  after  proteid 
(washed  meat)  ingestion  yielded  6.852  calories.  The  total  calo- 
rific value  of  one  gram  of  beef  muscle  when  Rubner  burned  it 
in  the  calorimeter  was  5.345  calories.  He  had  now  the  principal 
data  required  to  determine  its  heat  value  in  the  body.  If  from 
100  grams  of  meat  2.7  grams  appear  as  feces  having  a  calorific 
value  of  6.127  calories  per  gram,  then  there  is  here  a  loss  of 
6.127  X  2.7  =  16.83  calories.  If  from  every  100  grams  of  meat 
containing  15.4  grams  of  nitrogen  15.16  grams  of  the  latter 
appear  in  the  urine  and  such  urine  produced  by  ingesting  meat 
has  a  calorific  value  of  7.46  calories  for  every  gram  of  nitrogen 
present,  then  the  "energy  loss  in  the  urine  would  be  7.46  X 
15.16=  112.94.     For  dry  muscle  substance  we  find  therefore : 

Calories. 
100  grams  muscle 534-5 

Waste    (L"!!! 'IIT-,  ]  Total   129.77 


Feces 16.83 

Fuel  value  of  100  grams  of  dry  muscle 404-73 

From  this  value  there  must  be  a  slight  deduction  for  the  heat 
present  in  the  proteid  in  its  colloidal  state  but  lost  on  drying,  and 
for  the  heat  of  solution  necessary  to  dissolve  urea  and  other 
urinary  constituents.     Rubner  estimates  these  as: 

Heat  for  the  imbibition  of  proteid 2.688 

Heat  for  solution  of  urea r.989 

4.677 

Subtracting  4.67  from  404.73  leaves  400.06  calories  as  the 
maximum  of  energy  obtainable  from  100  grams  of  the  dried 


38  SCIENCE   OF   NUTRITION. 

solids  of  meat.  The  calorimeter  shows  a  heat  value  of  534.5 
calories  for  the  same  proteid.  Of  this,  400.06  calories,  or  74.9 
per  cent.,  is  available  in  the  organism,  while  the  remainder,  or 
25  per  cent.,  goes  to  waste. 

A  further  calculation  shows  that  every  gram  of  nitrogen  in  the 
urine  and  feces  represents  an  elimination  of  heat  from  proteid 
metaboHsm  equal  to  25.98  calories.  The  heat  value  of  proteid 
under  the  different  physiological  conditions  was  estimated  by 
Rubner  after  the  above  fashion,  and  may  thus  be  tabulated : 

CALORIFIC  VALUE  OF  PROTEID  IN  NUTRITION. 


After  proteid  (washed  meat)  ingestion 

After  meat  ingestion 

Starvation 


Heat     Value      of 

Calories    Yielded    Proteid      Metab- 

BY  Metabolism  of[   olism  Yielding   i 

100  Grams  OF  Pro-    Gm.  of  N  in  the 

TEiD  in  the  Body.    Excreta. 


26.66 

25-94 
24.94 


If  we  know  the  amount  of  nitrogen  in  t|je  excreta  we  can 
calculate  from  these  standard  figures  of  Rubner  the  heat  value 
of  the  proteid  metabolism  to  the  body.  Rubner  found  that  the 
heat  value  of  i  gram  of  pig's  fat  (lard)  was  9.423  calories. 
Since  this  fat  contains  76.5  per  cent,  of  carbon,  it  could  be  calcu- 
lated that  for  every  gram  of  carbon  eliminated  in  the  respiration, 
which  was  the  result  of  fat  metaboHsm,  12.3  calories  must  have 
been  liberated  in  the  body.  These  figures  enabled  Rubner  to 
calculate  the  amount  of  heat  liberated  by  the  fasting  man  of 
Pettenkofer  and  Voit,  whose  metaboHsm  we  have  already  dis- 
cussed. The  N  excreted  was  multipHed  by  24.94,  and  the  fat 
carbon  by  12.3  which  gave  the  total  heat  value  of  the  period : 

Heat  from  proteid  (11.33  Gm.  NX 24.94  Cal.) 283 

Heat  from  fat  (169.95  ^X  12.3  Cal.) 2091 

Total  heat  value  of  the  metabolism  as  calculated 2374 

Rubner  appHed  such  calculations  as  these  to  the  material  at 
hand  in  the  Hterature  of  the  time,  and  discovered  that  the  heat 
value  of  the  metabolism  of  the  resting  individual  was  propor- 


INTRODUCTORY.  39 

tional  to  the  area  of  his  body.  For  example,  a  man  in  starva- 
tion, or  on  a  medium  diet,  an  infant  at  the  breast,  and  a  starving 
dog,  were  shown  to  give  off  similar  quantities  of  heat  per  square 
meter  of  surface.  To  these  Rubner  subsequently  added  the 
results  of  his  researches  upon  a  dwarf.  The  following  tables 
illustrate  this  point  : 

Yield  of  Calories  per  Sq.  M. 
Surface  in  24  Hours. 

Adult  man  in  starvation 1134 

Dog  in  star^^ation 1112 

Adult  man  on  a  medium  mLxed  diet 1 1S9 

Breast-fed  infant 1221 

Dwarf  (weight  =  6.6  Kg.)  medium  mixed  diet 1231 

This  law,  that  the  resting  animal  in  starvation  or  on  a  me- 
dium diet  gives  off  the  same  quantity  of  heat  per  square  meter  of 
surface,  can  be  extended  so  that  it  appHes  to  all  warm-blooded 
animals.  Thus  E.  Voit^  has  collected  data  for  the  following 
table : 

Weight  in  Kg. 

Pig 128.0 

Man 64.3 

Dog 15.2 

Goose 3.5 

Fowl 2.0 

Mouse o.oiS 

Rubner  from  his  work  on  proteid  considered  that  the 
heat  value  of  i  gram  in  an  average  mixed  diet  might  well  be 
placed  at  4.1  calories.  Of  course,  such  a  mixed  diet  would 
contain  casein  (4.4  cal.),  the  organic  substance  of  meat  (4.233 
cal.),  and  vegetable  proteids  (3.96  cal).  The  daily  food 
allowance  for  animal  proteid  was  put  at  60  per  cent.,  for 
vegetable  proteid  at  40  per  cent.,  of  the  total  proteid  in  the 
mixed  dietary.  For  the  value  of  neutral  fats  Stohmann's  figures 
for  olive  oil,  animal  fat,  and  butter  fat  were  averaged  as  follows: 

Olive  oil 9-384  Calories  per  Gm. 

Animal  fat 9-372         "         "       " 

Butter  fat 9-i79         "         " 

Average 9-312         "         "       " 

^  E.  Voit:  " Zeitschrif t  fiir  Biologie,"  1901,  Bd.  xli,  p.  120. 


Calories. 

Per  Kilo. 

Per 

Sq. 

M.  Surface. 

19. 1 

1078 

32.1 

1042 

51-5 
66.7 

1039 
967 

71.0 

947 
1 188 

40  SCIENCE   OF  NUTRITION. 

For  the  heat  value  of  one  gram  of  fat  in  a  mixed  diet  Rubner 
therefore  adopted  the  value  9.3. 

The  follo\ying  heat  values  have  been  found  for  carbohydrates: 

Stohmann.     Rubner. 

Dextrose 3.692         3.755 

Milk  sugar 3877 

Cane  Sugar 3-959         4.001 

Starch 4.1 16 

Considering  the  predominating  importance  of  starch  in  the 
average  diet,  Rubner  gave  the  value  of  4.1  to  the  group  of 
carbohydrates  in  the  foods. 

Rubner's  "  standard  values"  have  been  widely  used  through- 
out the  world  in  determining  the  average  fuel  value  of  a  mixed 
diet.     They  are: 

1  gram  of  proteid 4.1  calories 

I  gram  of  fat 9.3  calories 

I  gram  of  carbohydrate 4.1  calories 

Their  accuracy  has  been  lately  verified  by  Rubner  ^  in  the  most 
careful  manner. 

Atwatcr  and  Bryant '  have  sought  to  modify  this  standard 
value  and  offer  the  following  in  substitution: 

I  gram  of  proteid 4.0  calories 

I  gram  of  fat S.q  calories 

I  gram  of  carbohydrate 4.0  calories 

Atwater^  states  that  these  figures  are  absolutely  available 
in  computing  the  average  diet  (results  of  41 1  experiments).  The 
difference  between  the  tv>'o  standards  probably  lies  in  the  fact 
that  Rubner  gave  comparatively  pure  foods,  while  the  waste 
through  the  feces  in  Atwater's  diets  reduced  the  nutritive  avail- 
abihty.  Another  difference  lies  in  the  fact  that  Atwater  *  uses 
as  a  small  calorie  the  amount  of  heat  necessary  to  raise  i  c.c.  of 

'Rubner:  "Zeitschrift  fiir  Biologie,"  Festschrift  zu  Voit,  1901,  Bd.  xlii, 
p.  261. 

'Atwater  and  Bryant:  "Report  of  the  Storrs  Agricultural  Experiment 
Station,"  1S99,  p.  no. 

^  Atwater:  "Am.  Journal  of  Physiology,"  1904,  vol.  x;  "Proceedings  of  the 
Am.  Physiol.  Society,"  p.  xxx. 

*  Atwater  and  Rosa:  U.  S.  Dept.  of  Agriculture,  Bulletin  63,  1899,  p.  55. 


INTRODUCTORY. 


41 


water  from  a  temperature  of  19.5°  to  20.5°   instead  of  from  0° 
to  1°,  the  unit  ordinarily  employed. 

Rubner/  still  working  in  the  jMunich  laboratory,  showed 
that  if  the  diet  were  increased  from  a  medium  to  an  abundant 
amount,  the  metaboHsm  as  indicated  by  the  heat  production 
rose.  This  dynamic  action  resulting  from  the  excessive  inges- 
tion of  a  foodstulT  w^as  greatest  with  proteid,  less  after  fat,  and 
scarcely  at  all  after  carbohydrates. 

Finally  Rubner,  in  his  ow^n  laboratory  at  Alarburg,  evolved 
an  animal  calorimeter  which  could  accurately  measure  the 
amount  of  heat  a  dog  produced  in  tw^enty-four  hours.  The 
dog  was  placed  within  the  chamber  of  the  calorimeter,  and  this 
chamber  was  attached  to  a  respiration  apparatus,  so  that  the 
metabolism  could  be  calculated  according  to  the  method  of 
Pettenkofer  and  Voit.  From  the  metabohsm  the  heat  produc- 
tion could  be  estimated.  The  results  were  a  triumphant 
demonstration  of  the  truth  of  the  law  of  the  conservation  of 
energy.  The  amount  of  heat  that  Rubner"  calculated  should 
have  been  derived  from  the  metabolism  of  the  dog  during  the 
day  spent  in  the  calorimeter  was  the  amount  actually  given  off  by 
the  dog  to  the  calorimeter.  The  metabolism,  the  cau  se  of  the  mo- 
tions of  hfe,  was  the  source  of  the  heat-loss  of  the  body.  The  re- 
sults achieved  constitute  a  final  verification  of  the  methods  of  cal- 
culating the  total  metabohsm  originated  by  Pettenkofer  and  Voit. 

An  epitome  of  Rubner's  experiments  is  here  presented: 


COMPARISON  OF  ESTIMATED  HEAT  FROM  METABOLISM  WITH 
HEAT  ACTU.ALLY  PRODUCED. 


Food. 

XUMBER    of 

Days. 

Heat  Calo. 

FROM 

Metabolism. 

Heat  Directly 
Determined. 

Difference 
IN   Percent- 
age. 

Starvation 

Fat 

f      5 
\      2 

f      1 

1    12 
[      6 

1,      7 

1296.3 
1091.2 
1510.1 
2492.4 
3985-4 
2249,8 
4780.8 

1305-2 
1056.6 
1498.3 
2488.0 

3958-4 
2276.9 

47^9-3 

—1.42 
—0.97 

—0.42 

Meat  and  fat 

Meat 

-1-0.43 

^  Rubner:  "  Sitzungsberichte  der  bayer.  Akademie,"  1885,  p.  454. 
-  Rubner:    "Zeitschrift  fiir  Biologie, "  1893,   Bd.  xxx,  p.  73. 


42  SCIENCE   OF   NUTRITION. 

Following  Rubncr,  Atwater,  at  one  time  a  pupil  of  Voit, 
with  the  aid  of  Rosa,  the  physicist,  has  constructed  a  large 
calorimeter  capable  of  measuring  to  a  nicety  the  amount  of  heat 
given  off  by  a  man  living  in  it.  This  apparatus  has  confirmed 
Rubner's  experiments  and  has  shown  that  the  energy  expended 
by  a  man  in  doing  any  work,  such  as  bicycle-riding,  is  exactly 
equal  to  the  energy  set  free  by  metabolism  in  the  body.  Ex 
nihil 0  nihil  fit. 

This  apparatus  was  the  product  of  many  years  of  labor  and 
its  cost  was  borne  by  the  United  States  Government.  Armsby 
has  completed  a  similar  one  for  use  with  cattle,  for  the  Agricultural 
Station  of  the  State  of  Pennsylvania.  These  elaborate  and 
costly  devices  pro\T  and  confirm  the  general  laws  of  metabolism 
in  the  body,  through  a  knowledge  of  which  alone  proper  systems 
of  nutrition  for  people  under  various  conditions  may  be  devised. 
The  American  Indian  when  first  shown  a  watch  thought  it  was 
alive.  We,  on  the  other  hand,  have  come  to  look  upon  the  liv- 
ing as  a  machine.  Like  the  moving  locomotive,  we  burn  more 
if  we  are  to  attain  a  faster  speed,  or  if  we  are  to  keep  all  parts 
warm  in  the  winter's  cold,  and  a  part  of  the  fuel  may  be  wasted  as 
heat.  In  both  cases  the  motion  and  the  heat  are  derived  from 
the  power  in  the  fuel.  The  casual  observer  sees  the  moving 
train,  but  the  expert  engineer  alone  knows  how  and  why  the 
wheels  go  around.  The  physiologist  busies  himself  answering 
the  similar  how  and  why  regarding  the  mechanism  of  living 
things. 

Before  taking  up  the  details  of  the  work,  we  may  copy  the 
last  general  pronouncement  of  Voit  ^  upon  the  subject  of  metab- 
olism.    It  reads: 

"The  unknown  causes  of  metaboHsm  are  found  in  the  cells 
of  the  organism.  The  mass  of  these  cells  and  their  power  to 
decompose  materials  determine  the  metabohsm.  It  is  abso- 
lutely proved  that  proteid  fed  to  the  cells  is  the  easiest  of  all  the 
foodstuffs  to  be  destroyed,  next  carbohydrates,  and  lastly  fat. 
The  metabolism  continues  in  the  cells  until  their  power  to 

*Voit:  "Miinchener  medizinischeWochenschrift,"  1902,  Bd.  xlix,  p.  233. 


INTRODUCTORY.  43 

metabolize  is  exhausted.  All  kinds  of  influences  may  act  upon 
the  cells  to  modify  their  abihty  to  metabolize,  some  increasing 
it  or  others  decreasing  it.  To  the  former  category  belong 
muscular  work,  cold  (in  warm-blooded  animals),  abundant 
food,  and  warming  the  cells.  To  the  latter,  cooling  the  cells, 
certain  poisons,  etc. 

"In  speaking  of  the  power  of  the  cells  to  metabohze,  I  have 
not  meant  thereby,  as  may  be  seen  from  all  my  writings,  that  the 
cells  must  always  use  energy  in  order  to  metabolize,  but  rather 
I  have  understood  thereby  the  sum  of  the  unknown  causes  of  the 
metabolic  ability  of  the  cells — as  one  speaks  of  the  fermen- 
tative 'power'  of  yeast  cells. 

"The  metabohsm  of  the  different  foodstuffs  varies  with  the 
quality  and  quantity  of  the  food.  Proteid  alone  may  burn,  or 
httle  proteid  and  much  carbohydrates  and  fat.  I  have  deter- 
mined the  amount  of  the  metabolism  of  the  various  foodstuffs 
under  the  most  varied  conditions.  All  the  functions  of  metab- 
ohsm are  derived  from  the  processes  in  the  cells.  In  a  given 
condition  of  the  cells,  available  proteid  may  be  used  exclusively 
if  enough  be  furnished  them.  If  the  power  of  the  cells  to  metab- 
olize is  not  exhausted  by  the  proteid  furnished,  then  carbo- 
hydrates and  fats  are  destroyed  up  to  the  hmit  of  the  ability  of 
the  cells  to  do  so. 

"  From  this  use  of  materials  arise  physical  results,  such  as 
work,  heat,  and  electricity,  which  we  can  express  in  heat  units. 
This  is  the  power  derived  from  metabohsm. 

"It  is  possible  to  approach  the  subject  in  the  reverse  order,, 
that  is,  to  study  the  energy  production  (Kraftwechsel)  and  to 
draw  conclusions  regarding  the  metabohsm  (Stoffwechsel).  It 
is  perfectly  possible  to  say  that  the  requirement  of  energy  in  the 
body  or  the  production  of  the  heat  necessary  to  cover  heat  loss, 
or  for  energy  to  do  work,  are  controlling  factors  over  the  metab- 
olism; since  on  coohng  the  body  or  on  working  correspond- 
ingly more  matter  is  destroyed.  But  one  must  not  conclude 
that  the  loss  of  body  heat  or  muscular  work  are  the  immediate 
causes  of  this  increased  metabolism.     The  causes  he  in  the 


44  SCIENCE   OF   NUTRITION. 

peculiar  conditions  of  the  organism,  and  muscle  work  and  loss 
of  heat  are  merely  factors  acting  favorably  upon  those  causes, 
raising  the  power  of  the  cells  to  metabolize.  In  virtue  of  this 
more  is  destroyed,  and  secondarily  the  power  to  work  and  in- 
creased heat  production  is  afforded. 

"The  requirement  for  energy  cannot  possibly  be  the  cause 
of  metabolism,  any  more  than  the  requirement  for  gold  will  put 
it  in  one's  pocket.  Hence  the  production  of  energy  has  a  very 
definite  upper  limit,  which  is  afforded  by  the  ability  of  the  cells 
to  metabolize.  If  the  cells  will  metabolize  no  more,  then  fur- 
ther increase  of  work  ceases  even  in  the  presence  of  direst 
necessity;  and  this  is  also  the  case  with  the  heat  production, 
even  though  it  were  very  necessary,  and  we  were  likely  to  freeze. 

"I  therefore  maintain  my  'older'  point  of  view,  that  of  pure 
metabohsm,  in  order  to  explain  the  phenomena  of  nutrition.  I 
am  convinced  that  it  is  the  right  way,  and  that  the  clearest  and 
most  unifying  development  will  be  possible  as  one  investigates 
what  substances  are  destroyed  under  different  circumstances, 
such  as  work,  and  loss  of  heat,  and  how  much  of  the  different 
materials  must  be  fed  to  maintain  the  body  in  condition." 


CHAPTER  II. 
THE    FECES. 

In  the  historical  introduction  of  the  preceding  chapter  it  has 
been  shown  that  the  nitrogen  of  the  urine  and  feces  can  be  made 
a  measure  for  the  determination  of  proteid  metaboHsm.  It  is 
easy  to  comprehend  that  urinary  constituents,  such  as  urea,  uric 
acid,  the  purin  bases,  creatinin,  etc.,  are  derived  from  the  metab- 
ohsm  of  flesh  in  the  body,  whether  the  flesh  be  the  body's  own 
or  that  of  an  animal  fed  to  it.  But  the  intestinal  canal  where 
the  feces  are  formed  is  a  long  tube  open  at  both  ends,  through 
which  may  pass  the  nitrogen  gas  of  the  air  swallowed  and  in- 
digestible substances  such  as  hair,  tacks,  etc.  In  diarrhea  the 
curds  of  milk,  pieces  of  undigested  meat  or  bread,  and  large 
quantities  of  fat  are  in  evidence.  These  common  observations 
would  seem  to  justify  the  popular  supposition  that  normal  feces 
are  made  up  of  the  undigested  residues  of  the  foodstuffs.  In 
truth,  however,  this  is  very  far  from  the  fact.  The  feces  are 
chiefly  the  unabsorbed  residues  of  intestinal  excretions. 

The  collection  of  the  feces  for  a  given  period  of  nutrition  is 
more  difficult  than  the  collection  of  the  urine.  The  urine  may 
be  collected  every  two  hours  and  may  fairly  represent  the  pro- 
teid metabolism  of  the  time,  but  the  feces  are  normally  passed 
but  once  a  day  by  a  man  on  a  mixed  diet,  and  only  once  in 
five  days  by  a  dog  fed  with  meat.  Furthermore,  particles 
fed  to  a  man  are  not  passed  in  his  feces  for  two  or  three 
days.  The  feces  formed  during  a  certain  digestive  period 
might  therefore  leave  the  body  two  or  three  days  after  the  urine 
was  dra\Mi  from  the  bladder.  To  obtain  clear  results  Voit 
fed  a  dog  with  60  grams  of  bones  in  a  preliminary  diet 
eighteen  hours  before  the  regular  feeding  began.  These  bones 
yielded  a  whitish  mark  in  the  fecal  excretion.     All  feces  sub- 

45 


46  SCIENCE   OF  NUTRITION 

sequent  to  the  mark  were  attributed  to  the  diet  used  in  the  ex- 
periment. At  the  conclusion  of  the  experiment  a  second  diet 
containing  bones  was  given.  The  whitish  excrement  formed 
from  this  indicated  the  end  of  the  feces  of  the  period.  For  the 
same  purpose  Rubner  ^  gave  milk  (2  liters)  to  a  man,  the  last 
portion  of  the  milk  being  taken  eighteen  hours  before  the  com- 
mencement of  a  period  of  feeding.  The  milk  feces  give  a  dis- 
tinct whitish  dividing  line.  A  teaspoonful  of  lampblack  may 
also  be  readily  made  use  of  in  man  and  in  animals.  Cremer  ^ 
uses  freshly  precipitated  silicic  acid  (10  to  25  grams  mixed  with 
40  to  100  grams  fat)  instead  of  bones.  This  gives  excellent 
results,  as  it  avoids  the  gelatin  nitrogen  in  the  bones,  and  is  of 
great  advantage  if  the  calcium  or  other  ash  constituents  of  the 
feces  are  to  be  determined. 

In  the  fundamental  experiments  Voit  found  that  a  fasting 
dog  weighing  30  kilograms  excreted  1.88  grams  of  dry  fecal 
matter  per  day,  containing  0.15  gram  of  nitrogen.  Evidently 
these  starvation  feces  are  not  derived  from  the  food,  but  must  be 
derived  from  the  matter  passed  from  the  body  into  the  intestinal 
canal.  An  analogous  condition  is  found  in  the  intestinal  tract 
of  the  new-born  infant.  The  meconium  consists  principally 
of  the  unabsorbed  residues  of  the  bile,  of  glycocholic,  taurocholic, 
and  fellic  acids,  of  cholesterin  and  lecithin,  colored  by  bilirubin 
or  biliverdin.  The  absence  both  of  putrefaction  and  the  acid 
of  the  gastric  juice  prevents  the  breaking  up  and  reabsorption 
of  many  of  these  substances,  processes  which  occur  soon  after 
birth.  The  fasting  dog  of  30  kilograms,  mentioned  above, 
excreted  1.88  grams  of  dry  feces,  but  a  fasting  dog  of  20.3 
kilograms  may  yield  4.3  grams  of  dry  bile  sohds  in  twenty- 
four  hours.^  The  ordinary  starvation  feces  therefore  cannot 
consist  of  the  total  of  the  excretions  from  the  body  into  the 
digestive  tract,  but  rather  their  unabsorbed  remainder. 

When  meat  was  given,  Bischoff  and  Voit  ^  found  that  the 

'  Rubner:  "Zeitschrift  fiir  Biologic,"  1879,  Bd.  xv,  p.  119. 

^  Cremer:  Ibid.,  1897,  Bd.  xxxv,  p.  391. 

'Voit:  Ibid.,  1894,  Bd.  xxx,  p.  548. 

*  Bischoff  and  Voit:  "Die  Ernahrung  des  Fleischfressers,"  i860,  p.  291. 


THE    FECES.  47 

production  of  feces  was  not  proportional  to  the  amount  of  meat. 
The  following  table  illustrates  the  average  amount  of  dry  feces 
produced  by  a  dog  weighing  35  kilograms  after  feeding  different 
quantities  of  meat: 

Meat  in  Grams.  Dry  Feces. 
500  10.7 

1800  1 1.2 

2500  11.93 

The  feces  had  the  same  pitch-black  color  as  starvation  feces 
and  were  similar  to  the  2  grams  of  feces  which  would  have  been 
produced  by  the  same  dog  had  he  been  starving.  No  muscle 
fibers  and  no  proteid  could  be  detected.  It  seemed  clear  that 
the  meat  feces  differed  from  the  starvation  feces  mainly  in 
quantity,  and  that  this  quantity  was  larger  because  the  secre- 
tions into  the  intestines  had  been  stimulated  by  the  passing  food. 

Fat  ingested  with  the  meat  in  moderate  quantities  had  no 
influence  on  the  feces.  Nor  had  sugar,  unless  its  fermentation 
produced  diarrhea.  Bread  somewhat  increased  the  volume  of 
the  feces,  which  contained  some  undigested  starch.  Here  an 
irritation  of  the  intestinal  canal  by  the  bread  produced  a  larger 
excretion  into  the  intestine. 

The  source  of  the  feces  was  further  investigated  by  Fritz 
Voit,^  who  separated  a  loop  of  the  intestine  about  a  third  of  a 
meter  long  from  the  rest  of  the  intestine  of  a  starving  dog.  Both 
ends  of  the  loop  were  tied  and  the  loop  remained  in  the  abdo- 
men in  connection  with  its  normal  nerve  and  blood  supply. 
The  two  ends  of  the  remaining  portion  were  resected.  After  a 
few  days  food  could  be  given  and  the  normal  excretion  of  feces 
took  place.  After  three  weeks  the  animal  was  killed.  It  was 
found  that  the  isolated  loop  contained  a  thick,  fecal-looking 
mass.  It  was  found  that  the  dry  solids  of  this  mass  contained 
the  same  percentage  of  nitrogen  as  did  the  feces  passed  by  the 
dog  during  the  three  weeks  of  the  experiment.  It  was  also 
calculated  that  the  amount  of  nitrogen  excreted  through  the 
wall  of  the  intestinal  loop  per  square  meter  of  its  surface  was 

'  F.  Voit:  "Zeitschrift  fiir  Biologic,"  1892,  Bd.  xxix,  p.  325. 


48 


SCIENCE   OF   NUTRITION. 


nearly  the  same  per  unit  of  area  as  the  amount  of  nitrogen  in 
the  feces  when  spread  over  the  surface  of  the  whole  of  the  re- 
sected intestine.     The  folio  wing  table  shows  this : 


Percentage  of  N 
IN  THE  Dry 
Substance. 


Feces. 


Dog  I   ';.62 

Dog  III 527 


Content 
OF  Loop. 


Grams  X  from  i  Sq. 
M.iN  24  Hours. 


5-32 
6.88 


Feces. 


0.28 
0.25 


Content 
OF  Loop. 


0.32 


The  loop  contained  fat  and  fatty  acids  in  greater  quantity 
than  is  normally  found  in  feces,  which  may  indicate  a  usual 
reabsorption  of  these  substances. 

Fritz  Voit  has  therefore  sho\\Ti  that  the  excretion  of  sub- 
stances from  an  isolated  loop  of  the  intestine  produces  a  mass 
of  a  similar  constitution  and  of  nitrogen  output  equal  to  that 
in  the  normal  resected  intestine  of  the  same  animal  through 
which  meat  and  fat  were  passing.  He  therefore  concludes  that 
the  feces  are  derived  principally  from  the  substances  excreted 
through  the  wall  of  the  intestine.  The  nitrogen  so  excreted 
is  as  much  to  be  considered  a  product  of  proteid  metabolism  as 
is  the  nitrogen  of  urea.  It  is  regretable  that  very  little  is  known 
regarding  the  chemistr}^  of  these  nitrogenous  compounds  ex- 
creted into  the  intestine. 

It  has  been  seen  that  the  feeding  of  simple  foodstuffs,  such  as 
meat,  fat,  and  sugar,  scarcely  influenced  the  composition  of  the 
feces  in  the  dog.  In  herbivora  we  pass  to  another  extreme. 
Here  vast  amounts  of  cellulose  are  eaten,  a  great  part  of  which 
is  never  digested,  but  even  after  long  retention  in  the  capacious 
intestinal  tract  is  passed  in  the  feces.  After  giving  an  ordinary 
fodder  to  a  cow,  as  much  nitrogen  may  be  passed  in  the  feces  as 
in  the  urine.  Under  such  conditions  as  these,  the  very  volu- 
minous feces  evidently  do  consist  largely  of  the  undigested 
residues  of  the  fodder. 


THE    FECES.  49 

Concerning  the  fecal  production  in  man,  it  has  been  found 
that  Cetti"^  excreted  3.8  grams  of  dry  fecal  sohds  per  day  during 
a  fast  of  ten  days,  Breithaupt  2  grams,  and  a  medical  student^ 
2.2  grams,  less  in  reality  than  would  a  dog  of  similar  size, 

Rieder^  fed  a  man  on  a  diet  containing  starch,  sugar,  and 
lard  from  which  a  cake  was  baked.  The  food  contained  no 
nitrogen,  but  the  fecal  excretion  was  0.54,  0.87,  and  0.78 
gram  of  nitrogen  per  day,  contrasting  with  0.316  gram  from 
Cetti,  0.1 13  from  Breithaupt,  and  0.13  from  a  medical  student 
during  fasting.  The  food,  even  though  it  contains  no  proteid, 
stimulates  the  fecal  production. 

It  has  been  stated  that  Voit  early  noticed  the  occurrence  of 
starch  particles  in  the  feces.  A  large  number  of  experiments 
have  been  made  to  test  the  digestibility  of  the  various  vegetables 
and  cereals.  Rubner*  fed  an  able-bodied  soldier  on  3078 
grams  of  variously  cooked  potatoes  daily  and  found  pieces  of 
potatoes  in  the  feces.  He  notes  that  an  inhabitant  of  Ireland 
will  eat  4500  grams  of  potatoes  a  day.  Friederich  Miiller^ 
writes  that  after  feeding  a  large  quantity  of  bread,  the  feces  may 
have  practically  the  same  composition  as  bread. 

The  better  understanding  of  this  question  of  the  "digesti- 
bility" of  the  carbohydrates  has  come  through  the  work  of 
Prausnitz®  and  his  pupils,  Moeller  and  Kermauer.  Moeller 
found  that  no  starch  appeared  in  the  feces  after  feeding  well- 
cooked  white,  rye,  and  graham  bread,  rice  or  potatoes  (even  when 
fed  in  pieces)  or  legumes  when  they  were  prepared  in  the  form  of 
puree.  Legumes  not  in  the  form  of  puree,  such  as  string  beans 
eaten  as  salad,  may  resist  the  action  of  the  digestive  juices  so 
that  the  starch  contents  of  the  cell  is  untouched,  and  the  vegeta- 
ble cells  appear  in  the  feces.  These  facts  explain  the  appear- 
ance of  bread  in  the  feces  if  the  bread  be  badly  cooked,  or  if 

^  Lehmann,  Mijller,  I.  Munk,  Senator,  Zuntz:  "  Virchow's  Archiv,"  1893, 
Bd.  cxxxi.  Suppl.  Heft. 

^Johansson,  Landergren,  Sonden,  Tigerstedt:  "Skandin.  Archiv  fiir 
Physiologic,"  1896,  Bd.  vii,  p.  29. 

^  Rieder:  "Zeitschrift  fur  Biologic,"  1884,  Bd.  xx,  p.  378. 

*  Rubner:  Ibid.,  1879,  Bd.  xv,  p.  146. 

=  Fr.  Miiller:  Ibid.,  1884,  Bd.  xx,  p.  375. 

'Prausnitz:  Ibid.,  1897,  Bd.  xxxv,  p.  335. 


50 


SCIENCE   OF   NUTRITION. 


such  a  "heavy"  bread  as  pumpernickel  be  eaten.  The  im- 
perfectly cooked  bread  contains  starch  granules  whose  cover- 
ings are  impermeable  to  the  digestive  juices,  as  are  also  many 
of  those  in  the  unbolted  rye  of  pumpernickel. 

Prausnitz  finds  that  if  a  man  be  put  on  a  rice  diet  and  then 
meat  be  substituted  for  most  of  the  rice,  the  composition  of  the 
feces  does  not  vary  with  the  diet.  Such  feces  he  calls  nor- 
mal feces.  They  may  contain  a  negligible  quantity  of  libers  of 
meat  (Kermauer)  or  of  cellulose  from  the  rice. 

The  feces  of  six  persons  placed  alternately  on  meat  and  rice 
diets  yielded  normal  feces,  the  percentage  composition  of  whose 
drv  solids  was  as  follows : 


COMPOSITION   OF  FECES  ON  DIFFERENT  DIETS. 


No. 

Person. 

Principal  Food 

X5«. 

Ether  Extract  ;«. 

Ash  r*- 

I 

H. 

Rice 

8.83 

12-43 

15-37 

2 

H. 

Meat 

8.75 

15-96 

14.74 

3 

M. 

Rice 

8.37 

18.23 

11.05 

4 

M. 

Meat 

9.16 

16.04 

12.22 

5 

W.  P. 

Rice 

8.59 

15.89 

12.58 

6 

W.  P. 

Meat 

8.48 

17-52 

^3-^3 

7 

J.  Pa. 

Rice 

8.25 

14-47 

8 

J.  Pa. 

Meat 

8.16 

15.20 

9 

F.  Pi. 

Rice 

8.70 

16.09 

lO 

F.  Pi. 

Meat 

9-05 

15-14 

II 

Vegetarian. 

Rice 
Average, 

8.78 
8.65 

18.64 
16.39 

12.01 

13.82 

It  is  seen  from  this  that  whether  the  food  solids  contain  1.5  per 
cent.  N,  as  in  rice,  or  ten  times  that,  as  in  meat,  the  composition 
of  the  feces  remains  uninfluenced.  Normal  feces  result  from  the 
eating  of  any  food  which  is  completely  digested  and  absorbed. 
In  all  such  cases  these  feces  have  the  same  composition  and  are 
derived  from  the  intestinal  wall.  It  is  therefore  not  astonishing 
that  a  vegetarian  of  many  years'  standing  produced  the  same 
kind  of  feces  when  fed  on  rice  as  did  the  other  men.  The  same 
quality  of  feces  has  been  obtained  after  giving  good  bread. 

In  this  connection  it  is  interesting  to  note  that  the  heat  value 
of  one  gram  of  human  feces  is  very  constant  whether  the  person 


THE    FECES.  5 1 

is  on  a  meat  diet  or  a  medium  mixed  diet.  Rubner^  gives  the 
value  of  one  gram  of  organic  matter  in  the  feces  of  a  man  on  a 
meat  diet  at  6.403  cal.,  while  on  a  mixed  diet  one  gram  varies 
between  6.061  and  6.357  cal.  The  average  fuel  value  of  feces 
is  therefore  6.2  calories  per  gram  of  dry  organic  substance,  and 
this  changes  only  when  there  is  a  poor  utiHzation  of  the  food.^ 
According  to  Lorisch,^  one  may  calculate  the  approximate  heat 
value  of  feces  by  reckoning  the  nitrogen  therein  as  proteid,  and 
multiplying  the  "proteid,"  "fat"  and  carbohydrate  present,  by 
their  usual  heat  value.  The  sum  of  these  is  said  to  give  a  rough 
estimate  of  the  calorific  loss  through  the  feces. 

After  eating  pumpernickel,  bad  bread  or  string  beans  the 
waste  of  undigested  residues  of  these  substances  may  appear 
in  the  feces,  changing  its  composition  and  lowering  its  per- 
centage of  nitrogen  content. 

In  general,  Prausnitz  finds  no  difference  between  the  digesti- 
bility and  absorbability  of  animal  and  vegetable  foods.  Meat, 
rice,  and  bread  from  fine  flour  are  all  digested  and  absorbed. 
The  ordinary  feces  indicate  whether  a  given  food  is  a  small  or  a 
great  feces  builder,  not  how  much  or  how  little  food  has  been 
used  for  the  organism. 

The  value  in  such  foods  as  cabbage,  string  beans,  cauliflower 
and  the  hke  lies,  aside  from  their  flavor,  in  the  fact  that  their 
indigestible  waste  may  enhance  peristalsis  in  the  intestine. 
Their  food  value  is  small,  and  if  given  to  those  with  weak 
digestions,  is  dubious. 

^  Rubner:  "Die  Gesetze  des  Energieverbrauchs,"  1902,  p.  35. 

^  Rubner-.  Leyden's  "  Handbuch  der  Ernahrungstherapie,"  1903,  p.  32. 

^  Lorisch:  "  Zeitschrift  fur  physiologische  Chemie,"  1904,  Bd.  xli,  p.  308. 


CHAPTER  III. 

STARVATION. 

Starvation,  or  hunger,  is  the  deprivation  of  any  or  all  the 
elements  necessary  to  the  nutrition  of  an  organism.  Thus 
when  carbohydrates  and  fats  only  are  eaten,  proteid  hunger 
ensues.  If  the  body  is  deprived  of  water  or  of  calcium,  thirst 
and  calcium  hunger,  as  the  case  may  be,  follow.  Complete 
starvation  occurs  when  all  the  required  elements  are  inadequate. 
A  fasting  dog  to  whom  no  food  or  drink  is  offered  does  not  un- 
dergo starvation  in  this  sense,  for  a  dog  does  not  sweat  through 
his  skin,  as  is  the  case  in  man,  and  the  metaboHzed  tissue  fur- 
nishes enough  water  for  the  urine  and  respiration.  There  is 
also  no  water  hunger  in  a  dog  when  meat  is  ingested,  for  the 
meat  contains  enough  water  to  dissolve  the  end-products  of 
its  metaboHsm  in  the  urine. 

A  true  picture  of  water  hunger  is  presented  by  Straub/  who 
gave  a  dog  dry  meat  powder  mixed  with  fat.  Under  these  cir- 
cumstances water  is  withdrawn  from  the  tissues  to  dissolve  the 
urea  formed.  He  found  that  muscles  may  lose  20  per  cent,  of 
their  water  content  without  pathological  manifestations,  al- 
though withdrawal  of  water  somewhat  increased  the  proteid 
metaboUsm.  The  experiment  could  not  be  carried  to  the  point 
of  death  from  thirst,  for  after  a  few  days  the  food  was  regularly 
vomited,  on  account  of  the  decreased  flow  of  the  digestive 
secretions  and  an  altered  condition  of  the  intestinal  canal.  The 
non-absorption  of  the  meat  powder  threw  the  body  on  the  re- 
sources of  its  own  tissue,  and  this  form  of  starvation,  as  has  been 
shown,  does  not  constitute  water  hunger. 

Rubner  ^  finds  that  starving  pigeons  die  of  thirst  in  four  to 

'  Straub:  "Zeitschrift  fur  Biologic,"  1899,  Bd.  xxxviii,  p.  537. 

*  Rubner:  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1903,  p.  53. 

52 


STARVATION.  53 

five  days,  while  those  allowed  only  water  live  twelve  days. 
Water  hunger  is  therefore  more  quickly  fatal  than  starvation 
when  water  is  allowed.  Under  the  usual  conditions  of  so- 
called  starvation  experiments  water  is  freely  allowed,  so  that 
water  hunger  does  not  enter  as  a  factor  into  the  following  dis- 
cussion. 

If  water  be  available,  the  organism  obtains  the  energy 
necessary  for  its  continued  existence  from  the  destruction  of  its 
own  store  of  proteid  and  fat.  After  a  variable  length  of  time 
the  organism  succumbs.  Exposure  to  cold  greatly  hastens  the 
end.  What  is  ordinarily  called  death  from  starvation  is  often 
really  death  from  exposure. 

Sued  has  fasted  several  times  for  thirty  days.  Dr.  Tanner, 
an  American  physician,  for  forty  days;  and  Merlotti  in  Paris 
for  fifty  days.  Succi  took  laudanum  in  considerable  quantity 
to  stay  the  pain  in  his  stomach,  while  Merlotti  took  only  water. ^ 
The  effect  of  fasting  on  the  spirits  of  the  faster  varies  with  the 
individual.  Usually  there  is  a  loss  of  buoyancy  of  spirit,  a  de- 
creased desire  to  work,  and  a  decrease  in  the  actual  power  to 
work.  Succi,  however,  was  capable  of  considerable  exertion, 
such  as  walking  and  riding,  without  ill  effects.  A  dog  does  not 
manifest  the  same  depression  as  is  seen  in  man.  Dogs  may  be 
starved  several  days  before  they  are  run  in  a  hunt.  The  longest 
fast  on  record  is  that  of  Kumagawa's^  dog,  who  died  on  the 
ninety-eighth  day.  This  dog  was  reduced  in  weight  from  17  to 
5.96  kilograms,  a  loss  of  65  per  cent. 

The  day  to  day  history  of  the  starving  organism  must  now 
be  considered. 

In  the  first  days  the  amount  of  proteid  metabolized  depends 
upon  the  two  factors,  the  glycogen  content  of  the  individual  and 
the  quantity  of  proteid  ingested  before  the  starvation  period. 
The  influence  of  the  first  factor  was  shown  by  Prausnitz.^ 
Fifteen  individuals  (mostly  medical  students  who  were  taking 

^  Luciani:  "Das  Hungern,"  1890,  p.  28. 

^  Kumagawa  and  Hayashi:  "Archiv  fiir  Physiologic,"  1898,  p.  431. 

^  Prausnitz:  "  Zeitschrift  fiir  Biologic,"  1892,  Bd.  xxix,  p.  151. 


54 


SCIENCE   OF   NUTRITION. 


a  course  of  instruction  in  the  laboratory)  fasted  for  sixty  hours. 
The  first  day's  urine  was  collected  beginning  after  twelve  hours 
of  fasting.  The  second  day's  urine  contained  in  twelve  cases 
more  nitrogen  than  that  of  the  first  day  of  starvation.  The 
lower  proteid  destruction  on  the  first  starvation  day  must  have 
been  due  to  the  continued  use  of  sugar  from  the  glycogen  supply. 
It  is  known  that  the  combustion  of  sugar  considerably  reduces 
the  proteid  metabolism,  so  the  second  day  and  not  the  first  of 
starvation  should  be  taken  as  the  basis  of  the  fasting  proteid 
metabolism. 

The  second  factor,  or  the  influence  of  the  previous  meat  in- 
gestion, is  especially  dominant  in  dogs.  Voit^  fed  a  dog  weigh- 
ing 35  kg.  with  diflferent  quantities  of  meat  and  noticed  the 
effect  on  urea  elimination  during  subsequent  starvation.  The 
results  were  as  follows: 


INFLUENCE  OF    PREVIOUS    DIET  ON    UREA  ELIMINATION  IN 
STARVATION. 


Grams  of  Urea  Excreted  During  Starvation 
Following  Various  Diets. 


Meat, 
2500  G. 


Last  food  day 180.8 

ist  fasting  day 60.  i 

2d 

3d  " 
4th 

5th  " 
6th  " 
7th 

8th      " 
9th 
loth     " 


24.9 
19. 1 

17-3 
12.3 

^3-3 
12.; 


Meat,  1800 

G.;   Fat, 

250  G. 


130.0 
37-5 
23-3 
16.7 
14.8 
12.6 
12.8 
12.0 


Meat, 
1500  G. 


Meat, 
1500  G. 


110.8 
26.5 
18.6 

15-7 
14.9 
14.8 
12.8 

12.9 

12. 1 
II.9 
II.4 


Bread. 


24.7 
19.6 
15.6 
14.9 
13.2 
12.7 
13.0 


It  is  evident  from  this  that  on  the  sixth  day  of  starvation  the 
urea  ehmination  was  the  same  in  all  cases,  or  about  thirteen 
grams.  Voit,  however,  assumed  a  fasting  minimum  of  twelve 
grams  of  urea  per  day.     He  deducted  the  twelve  grams  from 

*  Voit:  "Zeitschrift  fiir  Biologic,"  1866,  Bd.  ii,  p.  307. 


STARVATION. 


55 


what  he  had  found  for  the  first  days  and  obtained  the  grams  of 
urea  which  were  derived  from  the  previous  food,  as  follows : 


UREA    ELIMINATION    IN     STARVATION    ATTRIBUTABLE     TO 
PREVIOUS  DIET. 


Meat, 
2500  G. 


Meat,  1800 

G.;  Fat, 

250  G. 


Meat, 

IsOO  G. 


Meat, 
1500  G. 


(Last  food  day) 
I  St  fasting  dav. 
2d  "  "  . 
3d        "         "  . 

4th       "  "   . 

5th       "  "    . 


(168.8) 
48.1 
12.9 
7-1 

5-3 
0-3 


(118.0) 

25-5 

II-3 

4-7 

2.8 

0.6 


(98.8) 

17.7 

6.2 

5-5 
2.9 

2.2 


(98.8) 

14-5 
6.6 

3-7 
2.9 
2.8 


(12.7) 
7.6 

3-6 
2.9 
1.2 
0.7 


The  amount  of  extra  proteid  metaboKsm  is  seen  from  the 
above  to  be  directly  dependent  on  the  previous  feeding,  a  com- 
mon level  being  reached  in  all  cases  on  the  fifth  day  of  fasting. 

These  experiments  led  Voit  to  differentiate  between 
"circulating  proteid,"  which  could  be  absorbed,  carried  to  the 
tissues,  and  burned,  and  "organized  proteid,"  which  was  the 
more  resistant  living  proteid  of  the  tissues  themselves.  Voit^ 
stated  that  in  metaboHsm  the  lifeless  proteid  furnished  to  the 
cells  by  the  blood  was  used  in  preference  to  the  living  organized 
tissue  proteid.  He  quoted  Landois's  experiments,  which 
show  that  after  producing  an  artificial  plethora  through  in- 
jection of  blood,  the  serum  proteids  are  readily  burned  and 
their  nitrogen  eliminated  in  the  urine,  while  the  red  blood-cells 
containing  the  organized  proteid  are  only  slowly  destroyed. 
If  serum  alone  be  transfused  its  proteid  is  rapidly  destroyed.^ 

Even  in  starvation  there  is  evidence  of  "circulating  proteid" 
as  food  for  the  tissues.  Thus  Miescher  showed  that  the  salmon, 
after  entering  the  Rhine  from  the  sea,  virtually  starves.  Yet 
the  genital  organs  of  both  male  and  female  greatly  develop, 
this  being  at  the  expense  of  the  muscles,  which  may  lose  55  per 
cent,  of  their  weight.     This  proteid  must  have  been  carried  to 

-  Voit:  "Handbuch  der  Ernahrung,"  1882,  p.  300. 

^  Forster:  "Zeitschrift  fur  Biologie,"  1875,  Bd.  xi,  p.  496. 


56  SCIENCE   OF   NUTRITION. 

the  various  parts  of  the  body  in  the  circulating  blood-stream, 
Miescher  finds  no  indication  of  any  destruction  of  muscle  fibers 
in  this  process  of  emaciation.  It  is  interesting  in  this  con- 
nection to  note  that  A.  R.  Mandcl^  has  been  able  at  a  pressure 
of  300  to  350  atmospheres  acting  on  lean  meat  seventy-two 
hours  old  to  press  a  fluid  containing  44  per  cent,  of  the  proteid 
present  in  the  fibers,  and  this  without  visible  change  from  the 
normal  histological  appearance  of  the  muscle. 

It  seems  quite  possible  that  in  ordinary  starvation  proteid 
from  the  muscle  and  other  tissue  passes  to  the  blood  and  is 
carried  to  all  the  organs  as  circulating  proteid  for  the  nutrition 
of  their  cells. 

In  modem  critical  consideration  of  the  "circulating  proteid" 
it  must  be  borne  in  mind  that  the  amino  products  resulting 
from  proteid  digestion  are  probably  largely  metabohzed  as  such, 
and  are  only  in  part  regenerated  into  proteid  within  the  organ- 
ism (page  291).  Since  the  composition  of  the  blood-plasma  is 
practically  the  same  in  starvation  as  after  large  digestion  of  meat 
(page  70),  it  is  evident  that  the  storage  of  such  regenerated 
proteid  must  be  effected  elsewhere  than  in  the  blood  (page  159). 

Another  thought  is  that  when  tissue  proteid  becomes  cir- 
culating proteid  in  the  cited  case  of  the  salmon,  modern  theory 
would  assume  its  cleavage  into  amino  acids  previous  to  its 
regeneration  into  the  tissue  proteid  of  the  genital  organs.  Thus 
Kossel"  estimates  that  a  salmon  weighing  9  kg.  deposits  at 
breeding-time  in  his  testicles  27  grams  of  salmin  containing 
22.8  grams  of  arginin.  Kossel  calculates  that  metabolism  of 
muscle  proteid  during  this  time  yields  ample  arginin  to  form 
the  new  salmin. 

Whatever  misconstruction  has  been  placed  on  Voit's  term 
"circulating  proteid,"  discussion  of  the  subject  has  served  to 
emphasize  the  distinction  between  the  behavior  of  living  tissue 
proteid  and  the  lifeless  proteid  (or  proteolytic  cleavage  products) 
of  the  nourishing  fluid. 

'  Mandel:  Unpublished  work  from  the  Munich  Clinic  of  Prof.  Fr.  Miiller. 
''Kossel:    " Biochemisches  Centralblatt, "  1906,  Bd.  v,  p.  33. 


STARVATION. 


57 


This  point  is  furthermore  strongly  illustrated  by  the  be- 
havior of  gelatin.  Voit  has  demonstrated  that  although  gelatin 
can  never  be  converted  into  tissue  proteid  nor  be  retained 
in  the  body,  its  ingestion  may  in  part  prevent  the  combustion 
of  the  Kving  proteid  tissue  of  the  body  (page  102). 

The  amount  of  proteid  metabolized  by  a  starving  animal  in 
good  condition  bears  quite  a  constant  relationship  to  the  total 
metabolism  involved.  Even  in  different  animals  this  constancy 
is  observed.  E.  Voit^  calls  attention  to  the  fact  that  the  nitrogen 
elimination  is  not  dependent  on  the  weight  of  the  animal,  since 
a  pig  of  115  kilos  produces  o.ii  gram  per  kilo,  whereas  a  guinea- 
pig  weighing  but  0.6  kilo  ehminates  0.65  gram  of  nitrogen  per 
kilo,  or  ten  times  as  much.  However,  a  comparison  of  the 
percentage  of  the  total  energy  derived  from  proteid  in  fasting 
animals  in  good  condition  (/".  e.,  with  considerable  fat)  varies 
within  much  narrower  limits  —  between  7.3  and  16.5  per  cent. 
This  is  shown  in  the  following  table : 


NITROGEN    METABOLISM     OF    DIFFERENT    ANIMALS     IN 
STARVATION. 


Weight   in 
Kg. 

?v   Elimination. 

Percentage 

Animal. 

Total. 

Per  Kg. 

Per  Sq.M. 
Surface. 

FROM     Pro- 
teid. 

Pig 

Man 

Dog     I 

Dog   II 

Dog  III 

Rabbit 

Goose 

Fowl 

Guinea-pig 

115. G 

63-7 
28.6 
18.7 

7-2 

2-7 

3-3 
2.1 
0.6 

6.8 
12.6 

is 

2.2 
1.2 
0.8 
0.7 

G.4 

0.06 

G.20 
G.18 
G.2G 
0.3G 
0.46 
0.23 

0-34 
G.65 

3-2 

6.4 

5-2 

4.6 

5-2 

4.8 

3-3 
4.2 
4.2 

7-3 
15.6 
13.2 

10.7 

13-5 
16.5 

7-4 
10. 0 
10.8 

It  is  evident  from  the  above  that  an  average  of  90  per  cent, 
of  the  energy  of  the  fasting  metabolism  may  be  supplied  by 
non-proteid  material.     This  material  is  fat  (see  page  26). 

If  a  fasting  organism  be  kept  at  the  same  temperature  and 
under   the   same    conditions    as   regards    the   performance  of 

'  E.  Voit:  "Zeitschrift  fiir  Biologie,"  iqgi,  Bd.  xli,  p.  iS8. 


58 


SCIENCE   OF   NUTRITION. 


external  work,  the  metabolism  is  remarkably  even  from  day  to 
day. 

Hanriot  and  Richet  ^  showed  the  even  absorption  of  oxygen 
and  ehmination  of  carbon  dioxid  during  the  early  days  of  fasting 
in  man,  as  is  illustrated  in  this  table : 

Liters  O9         Liters  COo 
PER  Hour.  per  Hour. 

After  17  hours'  fast 17.4  15.3 

"     24       "       "   16.85  14-15 

"     29       "       "   16.05  14-3° 

"     46      "       "   16.9  14.35 

Later  Lehmann  and  Zuntz  ^  made  some  experiments  on  the 
professional  faster  Cetti.  They  analyzed  his  urine  and  feces, 
and  also  obtained  two  samples  of  the  carbon  dioxid  eliminated 
between  lo  and  ii  A.  m.,  each  period  of  collection  lasting  from 
ten  to  fourteen  minutes.  In  other  words,  the  carbon  dioxid  out- 
put was  determined  for  only  twenty  to  twenty-six  minutes  daily. 
From  these  data  the  total  day's  metabolism  was  calculated. 
This  method  is  only  approximately  correct,  but  it  is  more  ac- 
curate in  the  even  metabolism  of  starvation  than  after  foods 
have  been  ingested.  In  this  method  the  lower  metabolism 
during  the  night  is  not  taken  into  consideration. 

The  investigation  of  the  metabolism  of  Cetti  during  a  ten 
days'  fast  was  as  follows : 

METABOLISM  OF  CETTI  IN  STARVATION. 


Fasting  Days. 

Proteid. 

Fat. 

Calories 

FROM 

Proteid. 

Calories 
FROM  Fat. 

Calories,      Calories 
Total.        per  Kilo. 

I  to  4 

5  to  6 

7  to  8 

9  to  10 

85.88 
69.58 
66.30 
67.96 

136.72 
131-.30 
149-35 
132-38 

329.8 
267.3 

254-7 
261. 1 

1288.2 
1237-4 
1407-3 
1247.4 

1 
1618              29.00 
1504              28.38 
1662              31.74 
1508             29.26 

A  very  careful  experiment  on  the  metabolism  of  a  fasting 
■medical  student  twenty-six  years  old  was  made  by  Johansson, 

*  Hanriot  et  Richet:  "Comptes  rendus  de  rAcademie  des  Sciences,"  1888, 
Tome  cvi,  p.  496. 

2  Lehmann  and  Zuntz:  "Arch.  f.  pathol.  Anat.,"  1893,  vol.  cxxxi,  Suppl. 
P-  23- 


STARVATION. 


59 


Landergren,  Sonden  and  Tigerstedt/  The  man  fasted  five 
days,  doing  light  work  in  the  respiration  apparatus.  The  metab- 
oHsm  during  these  days  was  determined.  The  excreta  in  grams 
were  as  follows: 


METABOLISM  OF  J.  A.   IX  STARVATION. 


N 

ELIilTNATION. 

C 

Eli 

VnNATTON*. 

Day  of 

Fasting. 

Urine. 

Feces. 

Total. 

Urine. 

Feces. 

Respiration. 

Total. 

I 

12.04 

0.13 

12.17 

8.0 

I.I 

1S8.5 

197.6 

2 

12.72 

0.13 

12.84 

8.3 

I.I 

179-4 

188.8 

3 

13.48 

0.13 

13.61 

9.9 

I.I 

172.2 

183.2 

4   

13-56 

0.13 

13.69 

10.3 

I.I 

169.4 

180.8 

5   

"■34 

0.13 

11.47 

9-3 

I.I 

165.8 

176.2 

The  evenness  of  the  carbon  and  nitrogen  ehmination  is 
remarkable.  From  the  above  figures  the  following  table  of 
the  general  metabohsm  is  made : 


Day  of  F.asting. 


Proteid  . 


I 76.1 

2 80.3 

3 85.1 

4 856 

5 71-7 


Fat. 


Calories 

FROM 

Proteid. 


206.1 
191. 6 
181. 2 
177.6 
181. 2 


303-5 
320.5 
339-4 
341-4 


Calories 

FROM 
F.AT. 


1916.9 
1781.9 
1684.7 
1651-9 
1684.7 


Calories, 
Tot.al. 


2220.4 
2102.4 
2024.1 
1992.3 
1970.8 


Further  calculation  shows  the  following  relations  between 
the  weight  of  the  individual  and  the  calorific  production : 


Day  of 
Fasting. 


Weight 
IN  Kilos. 

.  .66.99 


Calories 
PER  Kilo. 


.65.71 
.64.88 
.63.99 
-63-13 


■J-3 
.00 
.20 
-13 
-23 


On  the  fifth  day  of  fasting  it  is  seen  that  the  individual 
burned  71.7  grams  of  proteid,  181. 2  grams  of  fat,  and  produced 

^  "Skandin.  Archiv  fiir  Physiologie,"  1896,  Bd.  vii,  p.  54. 


6o 


SCIENCE   OF   NUTRITION. 


1971  calories,  or  31.23  calories  per  kilogram  of  body  substance. 
This  is  presumably  the  minimum  compatible  with  ordinary  Hfe. 
E.  Voit*  gives  the  following  summary  of    the  energy  re- 
quirements during  the  early  days  of  starvation  in  man: 


GENERAL  TABLE  OF  STARVATION  METABOLISM  IN  MAN. 


Energy  in  Calories. 

OF  Fast. 

Weight. 

Total. 

Per  Kg. 

PcrSq.M. 
Surface. 

.Author. 

I '      70.6 

1 704 

I  to  5 64.9 

1 59-5 

I  to  2 56.0 

2359 
2222 
2071 
1893 
1773 

334 
31.6 

31-9 
31.8 

31-7 

III2 
1060 
1042 
IOI2 
985 

Pettenkofer  and  Voit. 

Pettenkofer  and  Voit. 

Tigerstedt. 

Zuntz  and  Lehmann. 

Zuntz  and  Lehmann. 

This  minimal  metabolism  requirement  of  the  fasting  organ- 
ism appears  remarkably  constant  in  different  men.  Not  only 
is  the  total  metabolism  the  same  but  also  the  amounts  of  proteid 
and  fat  which  yield  the  energy  are  the  same.  This  is  shown  by 
comparing  the  nitrogen  excretion  of  the  different  fasters  during 
the  first  days.     These  are  as  follows: 

Cetti.2    Breithaupt.3   Succi.*         J.A.s  Succi.6 

1 13-55  lo-oi  13-81  12.17  17.00 

2 12.59  9.92  11.03  12.85  11.20 

3 13-12  13-29  13-86  13.61  10.55 

4 12.39  12.78  12.80  13-69  10.80 

5 10.70  10.95  12.84  11-47  11-19 

6 10.10  9.88  10.12  II. 01 

It  is  thus  evident  that  if  the  organism  has  previously  been  well 
nourished,  the  fasting  metabohsm  is  remarkably  even,  about 
13  per  cent,  of  the  total  energy  being  derived  from  proteid  and 
87  per  cent,  from  fat. 

'  Voit,  E:  "Zeitschrift  fiir  Biologic,"  1901,  Bd.  xli,  p.  114. 

^  Munk:  "Arch.  f.  Path.  Anat.,"  1893,  Bd.  c.xxxi,  Suppl.  p.  25. 

3  Munk:  Ibid.,  p.  68. 

*  Luciani:  "DasHungern,"  1890. 

*  Johansson,  Landergren,  Sonden  and  Tigerstedt:  "Skandin.  Archiv.  fiir 
Physiol.,"  1896,  Bd.  vii,  p.  54. 

*  E.  and  O.  Freund:  "Wiener  klinische  Rundschau,"  1901,  Bd.  xv,  p.  91. 


STARVATION. 


6i 


During  prolonged  fasting  the  nitrogen  output  sinks  much 
below  the  figures  of  the  earlier  days.  Thus  a  woman  twenty- 
four  years  old  averaged  4.15  gm.  from  the  thirteenth  to  the 
twenty-fifth  day  of  fasting.^  A  girl  nineteen  years  old  whose 
esophagus  had  been  occluded  by  drinking  sulphuric  acid  excreted 
2.8  grams  of  nitrogen  on  the  sixteenth  day  of  fasting."  An 
invahd  of  Tuczec's^  averaged  4,25  grams  of  nitrogen  between 
the  fifteenth  and  twenty-first  days.  Under  Luciani's  obser- 
vation, Sued  excreted  4.08  grams  on  the  twenty-ninth  day,  and 
under  E.  and  O.  Freund  his  nitrogen  excretion  was  2.82  grams 
on  the  twenty-first  day.  The  latter  authors  say  that  after  this 
there  was  a  sudden  rise  in  the  amount  of  nitrogen  and  chlorin 
in  the  urine,  suggesting  the  so-called  premortal  rise,  which  caused 
them  to  stop  the  experiment.  About  3  grams  of  nitrogen 
in  the  urine  or  a  daily  destruction  of  18.75  grams  of  proteid 
would  seem  to  be  the  lowest  extreme  of  proteid  metaboHsm  in 
the  emaciated  organism  after  a  prolonged  fast.  The  analyses 
by  E.  and  O.  Freund  of  Succi's  urine  during  a  fast  of  twenty-one 
days  is  the  most  complete  record  of  the  sort.  The  daily  nitrogen 
excretion  is  given  in  grams  below  : 


DAILY  NITROGEN  EXCRETION  OF  SUCCI  IN  STARVATION. 


Day 


1 17.0 

2 II. 2 

3 10.55 

4 10.8 

5 ii-iQ 

6 II. 01 

7 8.79 


Day. 


N. 


g 
10 
II 
12 
13 
14 


Day. 


9-7-1  15  5-05 

ro-o5!i6 4.32 

7-i2li7 5.4 

6.23I18 3.6 

6-84JI9 5-7 

5-I4120 3.3 

4.66I2I 2.82 


The  nitrogen  and  total  sulphur  ran  together  in  the  urine, 
in  the  proportion  of  17.3  N:  i  S.  Munk  found  the  relation 
g-  to  be  14.7  in  Breithaupt,  and  15. i  in  Cetti.     The  sulphur 

^  Seegen:  "Wiener  Acad.  Sitz.  Ber.,"  Bd.  xxxiii,  2  Abth. 
^  Schultzen:  "Virchow's  Archiv,"  1863,  p.  31. 
^  Tuczec:   "Arch,  fiir  Psychiatrie, "  Bd.  xv,  p.  764. 


62 


SCIENCE   OF   NUTRITION. 


is  believed  to  be  derived  exclusively  from  the  breaking  down  of 
proteid. 

The  nitrogen  and  total  phosphoric  acid  (PjOj)  in  the  urine  are 
not  found  in  the  same  relation  as  that  in  which  they  exist  in  meat 
(7.6:  i),  but  there  is  a  greater  phosphoric  acid  excretion.  This 
is  also  true  of  the  calcium  excretion.  This  greater  excretion  is 
due  to  the  metabohsm  of  the  bones  (Munk).  E.  and  O.  Freund 
found  that  the  pQ-  fell  from  5.7  on  the  first  day  of  Succi's 
starvation  to  between  4.2  and  4.4  during  the  subsequent  periods. 
Munk  found  this  value  to  be  4.4  in  Cetti  during  ten  days  and 
5.1  in  Breithaupt  during  six  days. 

A  partial  record  of  the  work  of  E.  and  O.  Freund  on  Succi 
is  given  below.  Their  analyses  of  the  urine  of  the  first,  third, 
eleventh,  and  twenty-first  days  of  starvation  are  in  part  repro- 
duced. 


COMPLETE  URINARY  ANALYSIS  OF  SUCCI  ON  FIRST,  THIRD, 
ELEVENTH,  AND  TWENTY-FIRST  STARVATION  DAYS. 


Day  of  Fasting. 


3d- 


Amt.  urine,  c.c 1435 

Total  N,  grams \      17.0 

Urea  N,  grams ,       14.8 


Uric  acid  N. 
Purin  base  N. 
Creatinin  N... 
Ammonia  N... 

Total  S 

Total  P2O,.  . . . 

CI 

Ca 

Mg 


0.29 
0.13 
0.134 
0.43 
3-2 
2.98 
14.9 
0.25 
0-33 


575 

10.55 
9-65 
0.20 
C.064 
0.198 
0.144 

1-3 

2.52 

2.56 


378 
6.32 

5-64 
0.075 
0.042 
0.372 

o.s'  * 
0.41 

1-51 
0.31 


235 
2.82 
1.65 
0.046 
0.034 
0.025 

O.IO 

0.64 

0.7 


Examination  of  the  above  will  show  that  whereas  in  the 
earlier  days  of  the  experiment  the  relationship  between  urea 
nitrogen  and  total  nitrogen  is  the  normal  of  about  85  per  cent., 
during  the  last  days  it  has  fallen  to  54  per  cent.  The  balance 
of  the  total  nitrogen  not  enumerated  above  is  made  up  of 
constituents  of  unknown  character.  The  Freunds  attribute 
great  significance  to  this  distribution  of  nitrogen  in  the  urine, 
which  was  noteworthy  between  the  sixteenth  and  the  twenty- 


STARVATION. 


63 


first  days.  A  similar  ratio  may  exist  in  the  urine  of  a  man 
unaccustomed  to  exercise  who  does  hard  work.^ 

The  relative  ammonia  excretion  was  apparently  the  same 
as  normal.  The  purin  bodies  ran  low.  The  chlorin  ex- 
cretion almost  vanished,  so  great  is  the  retentive  power  of  the 
body  for  its  sodium  chlorid  constituents.  Of  pathological 
substances,  the  urine  contained  acetone,  diacetic  acid,  urobiHn, 
and  dextrose.  The  dextrose  was  too  small  in  amount  to  be 
quantitatively  determined. 

A  communication  by  Brugsch,-  shows  that  the  quantities 
of  /3-oxybutyric  acid  and  acetone  in  the  urine  become  very  great 
in  extreme  hunger.  The  experiment  was  also  on  Succi, 
between  the  twenty-third  and  the  thirtieth  days  of  starvation 
and  showed  the  following  remarkable  values: 


ACETONURIA  IN  STARVATION  (SUCCI). 


Starvation  Day. 


N  IN  Grams. 


)3-oxybutyric 
Acid  in  Grams 


Acetone  in 
Grams. 


23d. 
24th 
25th 
26th 
27th 
28th 
29th 
30th 


5-87 
6.41 
6.27 
6.18 
6.30 

4-43 
4.19 

8.42 


9.24 
8.43 
9-85 
5.28 
11.62 
6.99 

9-15 
13.60 


0.569 
0.410 
0.463 
0.569 
0-525 
0.339 
0.242 
0.115 


The  excretion  of  urea  nitrogen  ran  between  54  and  70  per 
cent.,  and  the  ammonia  nitrogen  between  15.4  and  35.3  per 
cent,  of  the  total  nitrogen  in  the  urine.  The  high  ammonia 
neutralized  the  very  considerable  acidosis. 

Albumin  is  also  of  frequent  occurrence  in  the  starvation 
urine  of  man  and  animals. 

It  has  already  been  set  forth  that  the  general  metabohsm  is 
extremely  even  in  fasting,  and  it  may  be  added  that  existing 
evidence   shows   the   intermediary   metabolism  has   a  similar 

*  Jackson:  "Archives  italiennes  de  Biologie,"  1901,  Tome  xxxvi,  p.  463. 
^Brugsch:  "Zeitschrift  fiir  ex.  Pathologic  und  Therapie,"  1905,  Bd.  i,  p.  419. 


64 


SCIENCE   OF   NUTRITIOX. 


character.  Thus  Stiles  and  Lusk^  found  in  a  fasting  dog  made 
diabetic  with  phlorhizin  that  whereas  the  quantity  of  nitrogen 
and  sugar  ehminated  slowly  fell,  the  relation  between  the  two 
(the  Dextrose  :  Nitrogen  or  D:N  ratio)  remained  constant. 
This  is  shown  in  the  following  table: 


CONSTANT   RATIO    BETWEEN   DEXTROSE   PRODUCTION   AND 
N  ELIMINATION  IN  STARVATION. 


Period. 

D  PER  Hour. 

N  PER  Hour. 

D:i\. 

1 5  hours 

2.6l 

2-39 

2-51 

2".36 
2.32 

0-735 
0.720 
0.683 
0.666 
0.687 
0.670 
0.643 
0.642 

3-56 

6     "     

7       "       

12       "       

3.60 
365 

■i       "       

6     "     

7        "        

3.66 
3.62 

II        "        

The  hour  to  hour  sugar  production  from  proteid  is  therefore 
even  and  constantly  proportional  to  the  proteid  metabolism. 

Parker  and  Lusk^  showed  that  if  benzoic  acid  be  admin- 
istered as  lithium  benzoate  twice  a  day  to  a  fasting  rabbit  the 
animal  will  combine  it  with  the  glycocoll  of  its  metabohsm  in  such 
quantity  that  the  amount  of  the  resulting  hippuric  acid  bears  a 
constant  ratio  to  the  total  nitrogen  elimination  of  the  period.  In 
other  words,  there  is  a  constant  production  of  glycocoll  in  the 
organism  which  is  normally  burned,  but  which  in  this  case  is  com- 
bined with  benzoic  acid  and  eliminated  in  the  urine.  The  for- 
mula representing  the  formation  of  hippuric  acid  is  as  follows: 


CfiHsCOOH  +  NH2CH2COOH  =  CeH^CO.NHCHjCOOH  +  H^O 

Glycocoll.  Hippuric  Acid. 


Benzoic  Acid. 


The  results  of  the  experiment  indicate  a  production  of  3.98 
grams  of  glycocoll  from  the  metabolism  of  100  grams  of  body 
proteid.  The  following  table  begins  with  the  fifth  fasting  day 
and  the  second  of  benzoate  feeding,  and  is  as  follows: 

1  Stiles  and  Lusk:   ".\merican  Journal  of  Physiology,"  1903,  vol.  x,  p.  77. 
'Parker  and  Lusk:  Ibid.,  1900,  vol.  iii,  p.  478. 


STARVATION. 


65 


CONSTANT  RATIO  BETWEEN  GLYCOCOLL  PRODUCTION  AND 
N  ELIMINATION  IN  STARVATION. 


5  th  day  of  fast 
6th    "     "     " 
7th    "     "     " 
8th    "     "     " 
9th    "     "     " 


0.990 
1.087 

0-775 
1. 148 

0-515 


HiPPURIC 

Acid. 


0.7060 
0.6340 

0.4944 
0.5760 
0.3252 


Ratio  Hippuric  Acid    (or 

Glycocoll)    N:  Total   N. 


i:  18.0 
i:  21.6 
i:  19.8 
1:25.5 
i:  21.8 


The  average  ratio  is  i  :  21.5.  The  glycocoll  production 
seems  therefore  a  normal  and  constant  factor  of  the  proteid 
metabolism.  Horse's  urine  taken  at  random  showed  ratios  of 
1 :  15  and  1:17  (see  page  114). 

The  length  of  hfe  under  the  condition  of  starvation  generally 
depends  upon  the  quantity  of  fat  present  in  the  organism  at  the 
start.  The  quantity  of  fat  and  proteid  in  an  animal  at  the 
beginning  of  starvation  or  at  any  time  during  starvation  may  be 
estimated  if  the  day-to-day  metabohsm  be  determined  and  if 
the  whole  animal  be  analyzed  for  fat  and  proteid  at  the  time  of 
death.  The  sum  of  the  quantities  remaining  in  the  body,  and 
the  quantity  of  waste  of  previous  days,  will  give  the  composition 
of  the  animal  at  any  definite  date  during  the  experiment.  E. 
Voit^  shows  that  a  rabbit  with  an  original  fat  content  of  7  per 
cent,  lived  nineteen  days  and  lost  49  per  cent,  of  his  body  pro- 
teid. Another  rabbit  with  an  original  fat  content  of  only  2.3  per 
cent,  lived  but  nine  days  while  the  loss  of  body  proteid  amounted 
to  35  per  cent.  At  the  death  of  these  rabbits  the  amount  of  fat 
found  was  very  small,  and  the  general  vitality  toward  the  end 
was  almost  exclusively  maintained  by  the  combustion  of  proteid. 
Other  animals,  however,  which  lost  22  to  26  per  cent,  of  their 
proteid  contained  considerable  fat  at  the  time  of  death.  E.  Voit 
finds  that  the  greater  the  amount  of  fat  in  the  body,  the  less  the 
proteid  metabohsm.  In  animals  of  equal  fat  content  the 
relation  between  the  amount  of  fat  and  the  amount  of  proteid 
burned  in  the  cells  in  starvation  is  always  the  same.     When 


'  E.Voit:  "Zeitschrift  fur  Biologie  "  1901,  Bd.  xli,  p.  545. 


66 


SCIENCE   OF   NUTRITION. 


there  is  no  fat,  proteid  may  burn  exclusively.  From  this  it 
follows  that  the  quantity  oj  the  proteid  metabolism  in  starvation 
depends  upon  the  amount  of  jat  in  the  body. 

E.  Voit'  has  prepared  the  following  table  from  an  experiment 
of  Schondorff- upon  a  fasting  dog.  The  quotient  |^^-^^^ 
gives  the  ratio  between  these  two  components  of  the  organism 
at  the  time  specified.  The  ratio  ^?|fi^  gives  the  per- 
centage of  the  total  energy  derived  from  the  proteid  metabo- 
lism.    The  dog  died  on  the  thirty-eighth  day  of  his  fast. 


PROTEID    METABOLISM     IN     STARVATION    AS    INFLUENCED 
BY  THE    FAT    CONTENT    OF    THE    ANIMAL. 


Weight   in 
Kg. 

N  Content 

Excreta 

N 

IN  Gra.ms. 

Energy  per 
Sq.  Meter 
Surface. 

Energy  N 

Starvation 

Energy  Total. 
Reduced  to  ^. 

Day. 

Fat  Content. 

I  St   to    3d 

4th  to  13th. .. 
14th  to  15th. . 
16th  to  23d... 
24th  to  30th.. 
31st  to  35th.. 

36th 

37th 

38th 

22.4 
20.7 
19.7 
18.7 
17.4 
16.2 

15-7 
15-5 
15- 

0.25 
0.29 

0.34 
0.40 

0-57 
0.87 
1. 19 
1-34 
I-5I 

7.91 

5-38 

5-70 

5-71 
5-92 
6.62 
7.41 
8.41 
8.89 

1040 
974 
959 
944 
919 
go  I 
889 
887 
881 

26.5 
16.2 
18.1 
19. 1 
21.3 
25.6 

29-5 
33-8 
36.6 

E.  Voit  finds  that  the  amount  of  proteid  metabolism  depends 
so  absolutely  upon  the  relation  between  the  amount  of  fat  and 
proteid  in  the  body  (the  pl,"°ZTnd  that,  knowing  this 
ratio,  he  says  he  can  estimate  the  relative  proteid  metabolism. 
When  the  ratio  rises  to  4.84  in  the  rabbit,  then  98.3  per  cent,  of 
the  total  energy  may  be  derived  from  proteid.  Had  fat  still  been 
present  in  any  quantity  the  proteid  metaboHsm  would  have 
remained  low.  This  is  the  law  which  causes  the  gradual 
rise  in  the  proteid  metabolism  during  starvation,  the  "pre- 
mortal rise,"  it  has  been  termed.  The  increased  combustion 
of  the  proteid  is  due  to  the  requirement  for  energy  in  an  organ- 

'  E.  Voit:  Loc.  cit.,  p.  520. 

'  Schondorff:  "Pfliiger's  Archiv,"  1897,  Bd.  \x\ni,  p.  430. 


STARVATION.  67 

ism  which  has  a  constantly  decreasing  amount  of  fat  upon  which 
to  draw. 

The  actual  loss  of  body  weight  is  greater  when  proteid  is  the 
source  of  energy  than  when  the  energy  is  derived  from  fat.  The 
reason  for  this  is  that  if  one  gram  of  nitrogen  is  lost  there  is  a 
diminution  of  body  weight  of  ^t,  grams,  which  represents  just  so 
much  tissue  waste  and  an  energy  yield  of  0.8  calories  per  gram 
of  "flesh"  lost,  while  the  combustion  of  one  gram  of  fat  simply 
causes  the  loss  of  one  gram  in  body  weight  with  an  energy 
yield  of  9.3  calories.  To  obtain  equivalent  amounts  of  energy 
there  must  therefore  be  a  destruction  of  eleven  and  a  half  times 
more  "flesh"  by  weight,  than  when  fat  is  oxidized. 

What  is  the  cause  of  death  from  starvation?  It  does  not 
seem  to  be  due  to  an  essential  change  in  the  composition  of  the 
cells  themselves,  for  no  chemical  alteration  has  been  detected 
in  them.^  What,  then,  is  the  cause  of  death?  The  general 
argument  of  E.  Voit  is  as  follows:  It  must  be  due  either 
to  a  general  failure  of  all  the  cells  or  injury  of  certain  organs 
which  are  necessary  for  life.  If  the  first  cause  were  the 
true  cause,  then  death  would  take  place  when  a  certain  definite 
percentage  of  proteid  loss  occurred.  This  does  not  happen, 
since  the  body  loss  at  the  time  of  death  may  vary  between  20 
and  50  per  cent,  of  its  original  content  proteid.  When  the  genital 
organs  of  the  salmon  develop  at  the  expense  of  the  liquefying 
muscle  substance  brought  them  by  the  blood,  not  a  single  muscle 
cell  of  the  fish  is  killed,  even  though  these  lose  55  per  cent,  of  their 
proteid  in  the  process  (Miescher).  It  seems  extremely  improb- 
able, then,  that  a  much  smaller  loss  of  proteid  in  starvation  can  be 
the  cause  of  general  cellular  death.  On  the  other  hand,  if 
death  be  due  to  the  failure  of  certain  organs,  especially  important 
to  hfe,  the  cause  is  to  be  found  in  two  factors.  Either  these 
organs  receive  too  Httle  nutrition  for  their  proper  functioning, 
or  they  become  so  emaciated  that  they  fail  in  spite  of  sufficient 

^  Abderhalden,  Bergell,  and  Doerpinghaus:  "Zeitschrift  fur  physiologische 
Chemie,"  1904,  Bd.  li,  p.  153. 


68 


SCIENCE    OF   NTTRITION. 


nutriment.     Either  the  machine  wears  out  or  the  fuel  is  insuffi- 
cient for  it. 

The  following  table  gives  some  answer  to  this.  The  general 
arrangement  is  in  the  order  of  the  greater  original  fat  content  of 
the  animals : 

INFLUENCE  OF  FAT  CONTENT  ON  PROTEID  METABOLISM  AND 
ON  LENGTH  OF  LIFE  IN  STARVATION. 


Animal. 

First 

Weight, 

Kg. 

Fat  in  ii. 

Loss    IN   f. 

Days    be- 
foreDeath 
FROM  Star- 
vation. 

Start. 

End. 

Animal. 

Body  N. 

Dog 

Fowl 

Guinea-pig  . 

Dog 

Fowl 

Rabbit 

Rabbit 

Rabbit 

Fowl 

Rabbit 

Rabbit 

20.64 

1-95 
0.67 

23-05 
I.oo 

i-Si 
2-53 
2-34 
1.89 
2.08 
2.99 

19 
26 
16 

II 
9.1 
71 
6.3 
6.3 
2.7 

2-3 
2-3 

12 

5 
10 

1-7 
0-7 
0.4 

0-5 
0-5 
0.7 
0.4 
0.3 

28 
42 
38 
34 
39 
49 
44 
41 
34 
35 
32 

22 
26 
26 

35 
37 
49 
49 
45 
41 
38 
35 

30 
35 
10 

38 
12 

19 

19 

19 

9 

8 

9 

Falk. 

Schmanski. 

Rubner. 

Schondorff. 

Kuckein. 

Rubner. 

Koll. 

Rubner. 

Kuckein. 

Kaufman. 

Rubner. 

In  the  first  three  animals  a  large  amount  of  fat  was  present 
at  the  time  of  death,  and  this  had  prevented  a  great  tissue 
waste.  Abundant  food  was  therefore  available  for  the  cells. 
The  cause  of  death  seems,  therefore,  to  be  in  a  reduction  of 
activity  in  one  or  more  organs  important  for  life. 

Again,  if  the  proteid  loss  be  kept  down  by  administering  pro- 
teid  in  quantity  insufficient  for  the  heating  demands  of  the  organ- 
ism, the  animal  is  kept  hving  largely  on  his  own  fat.  Schultz  ^  in 
this  way  kept  two  dogs  alive  for  twenty-eight  and  thirty-eight  days, 
with  losses  of  body  nitrogen  amounting  to  only  1 8  and  7  per  cent,  of 
the  original  quantity.  The  fat  present  was  only  0.4  to  0.5  per 
cent,  at  the  end.  These  dogs  certainly  suffered  from  no  general 
loss  of  cell  tissue.  E.  Voit  concludes  that  death  from  starvation 
is  primarily  due  to  loss  0}  substance  in  organs  important  to  life, 
but  it  may  also  ensue  under  certain  circumstances  as  a  result  of 
deficient  nutrition  to  these  organs. 

^  Schtiltz:  "Pfluger's  Archiv,"  1899,  Bd.  Ix.xvi,  p.  379. 


STARVATION. 


69 


The  question  of  what  organs  are  attacked  in  starvation,  has 
attracted  attention.  Long  ago  Voit^  showed  that  the  muscles 
of  a  cat  which  starved  thirteen  days  lost  30  per  cent.,  while  heart, 
brain,  and  cord  lost  3  per  cent,  only.  In  normally  nourished 
animals  E.  Voit  finds  that  the  relative  weights  of  the  fat-free 
organs  in  animals  of  the  same  species  are  very  constant.  He  ^ 
uses  Kumagawa's^  results  to  show  what  percentage  the  different 
organs  represent  in  the  fat-free  organism  of  a  dog  before  and 
after  a  twenty-four  day  fast.  The  third  column  represents  the 
percentage  loss  of  the  fat-free  organ  in  starvation : 


LOSS  IN  WEIGHT  OF  DIFFERENT  ORGANS  DURING  STARVATION. 


Organ. 


Skeleton 

Skin 

Muscles 

Brain  and  Cord 

Eyes 

Heart 

Blood 

Spleen 

Liver 

Pancreas 

Kidney 

Genitals 

Stomach  and  intestine 
Lungs 


Fat-free  Animal  Contains  in 
Percentage  of  Weight. 


Well  Nourished. 


14.78 
10.30 

53-77 
0.94 
o.ii 

0.54 
7.14 

0-39 
3-98 
0-33 
0.66 
0.30 
5.81 
C.89 


Starvation. 


21.50 
11.29 

48.39 
I. II 
0.16 
0.69 

5-69 
0.26 

3-05 
0.19 

0.45 
0.23 
6.02 

0.97 


Fresh  Fat-free 
Organ  Loses  in 
Perce  nt age 
Weight  during 
a  24  Days' Fast. 


5 
28 


3 
16 

48 
57 
50 
62 

55 
49 
32 
29 


It  is  apparent  that  the  greatest  loss  is  from  the  glands  and  the 
least  from  the  skeleton.  The  activity  of  the  glands  is  greatly 
reduced  in  starvation.  Luciani  found  that  there  was  no  gastric 
juice  formed  during  Succi's  thirty-day  fast,  but  Langley  and 
Edkins  find  pepsinogen  stored  within  the  cells  of  the  gastric 
glands.     The  bile  flow  continues  up  to  the  death  of  the  person, 

^  Voit:  "Zeitschrift  fiir  Biologic,"  1866,  Bd.  ii,  p.  355. 
^  E.  Voit:  Ibid.,  1904,  Bd.  xlvi,  p.  195. 

^  Kumagawa:  "  Aus  den  Mittheil.  d.  med.  Fakultat  der  kais.  Japan.  Univ.," 
Tokio,  Bd.  iii,  No.  i. 


70 


SCIENCE   OF   NUTRITION. 


but  in  diminished  quantity,  corresponding  to  the  lack  of  food 
and  the  decreasing  size  of  the  Hver.  The  writer  ^  has  noticed  a 
great  reduction  in  the  activity  of  the  milk  secretion  in  starving 
goats,  there  being  a  permanent  cessation  of  flow  after  five  days. 
The  percentage  of  fat  increases  in  the  milk,  as  it  does  in  the 
blood,  Hver,  and  other  organs."  The  fasting  organs  attract  fat 
from  the  fat  deposits  of  the  body  and  it  is  brought  to  them  by 
the  circulating  blood.  Dextrose  is  present  in  the  blood  up  to 
the  last  day  of  hfe,  having  its  probable  origin  in  a  constant 
production  of  sugar  in  proteid  metabolism.  The  composition 
of  the  plasma  of  the  blood  in  fasting  as  regards  its  proteid  con- 
stituents varies  very  slightly  from  the  normal.  Lewinski^ 
gives  the  following  comparative  analyses  of  blood-plasma  of 
dogs: 


loo  C.C.  BLOOD-PLASMA  CONTAIN  OF  GRAMS  N: 


Dog  I  ... 
Dog  II... 

Dog  III.. 
Dog  IV.. 


Fasting. 
Fed  . . . 
Fasting. 
Fed.... 


Total. 


0-935 
0.831 

0.921 
1.062 
1. 010 
0.977 


Fasting 

Fed 

Fasting i      1.096 

Fasting 1      1.052 

Fed I      0.877 


Albumin.      Globulin.   Fibrinogen 


0.621 
0.5 1 1 

0-313 
0-515 
0.467 
0-475 
0-554 

0536 
0.542 


0.257 
0.240 

0.544 
0.423 

0.450 
0.402 
0-443 
0.324 
0.248 


0.057 
0.080 
0.064 
0.124 
0.093 

O.IOO 

0.099 
0.192 
0.087 


The  only  constant  change  seems  to  be  a  slight  increase  of 
globulin  during  fasting.  Burckhardt  beheves  this  to  be  due  to 
the  passage  of  globuhns  from  the  tissues  to  the  blood.  Thus 
myosinogen,  the  principal  proteid  of  muscle,  may  pass  to  the 
blood,  possibly  to  become  serum  globulin  and  maintain  the 
normal  proteid  content  of  the  nourishing  fluid  of  the  body.  The 
percentage  of  hemoglobin  and  the  number  of  blood-corpuscles 
is  not  appreciably  affected.     It  is  evident  then  that  the  blood  in 

*Lusk:  Voit's  Festschrift,  "Zeitschrift  fiir  Biologie,"  1901,  Bd.  .xlii,  p.  41. 
^  Rosenfeld:  "Ergebnisse  derPhysiologie,"  1903,  Bd.  ii,  i,  p.  50. 
^  Lewinski:  "Pfliiger's  Archiv,"  1903,  Bd.  c,  p.  631. 


STARVATION.  71 

starvation  retains  the  normal  composition  as  regards  its  nutrient 
materials,  except  that  it  carries  fat  in  increased  quantity  to 
the  cells.  In  general  the  cells  are  well  nourished  for  the 
ordinary  maintenance  of  the  hfe  functions.  Hence  the  appetite 
is  not  an  expression  of  general  cellular  hunger,  but  rather  the 
result  of  a  local  condition  of  the  gastro-intestinal  canal,  which 
stimulates  the  individual  to  constant  replenishment. 

The  glycogen  of  an  animal  is  greatly  reduced  during  star- 
vation, but  after  twenty  days  it  is  not  entirely  removed.^  Praus- 
nitz^  reports  that  a  dog  weighing  22  kilograms,  after  fasting  for 
twelve  days  and  after  excreting  287  grams  of  sugar  in  the  urine 
brought  about  by  phlorhizin  injections,  still  contained  25  grams 
of  glycogen  in  his  body.  The  \mter^  has  found  0.4  gram  of 
glycogen  in  the  hver  of  a  meat-fed  phlorhizinized  dog  after 
eleven  days  of  diabetes  and  an  excretion  of  over  600  grams  of 
sugar.  Exercise  will  greatly  reduce  the  glycogen  content,  but 
the  only  method  of  completely  freeing  the  organism  of  glycogen 
is  by  tetanus.*  Zuntz^  rid  a  rabbit  of  glycogen  by  strychnin 
convulsions  and  then  kept  the  rabbit  fasting  and  under  the 
influence  of  chloral  for  119  hours.  During  this  time  5.25 
grams  of  sugar  were  excreted  in  the  urine  and  yet  1.286  grams  of 
glycogen  were  found  in  the  liver  and  muscles.  This  must  have 
gradually  arisen  from  the  proteid  metaboHsm.  The  writer" 
made  an  observation  that  in  a  fasting  diabetic  rabbit  tetanus 
produced  an  extra  elimination  of  sugar  in  the  urine  of  i.i  grams, 
which  undoubtedly  was  derived  from  the  glycogen  content  of  the 
organism.  The  quantity  ehminated  corresponded  to  the 
amount  found  as  glycogen  by  Zuntz  as  above  mentioned. 

There  now  remains  a  discussion  of  the  influence  of  work  and 
of  change  in  temperature  upon  the  fasting  organism. 

^  Kiilz:  Ludwig's  Festschrift,  1891,  p.  117. 

^  Prausnitz:  "Zeitschrift  fiir  Biologic,"  1892,  Bd.  xxix,  p.  168. 

^  Reilly,  Nolan  and  Lusk:  "American  Jour,  of  Physiol.,"  1898,  vol.  i,  p.  397. 

^  Kiilz:  Lud-nig's  Festschrift,  1891,  p.  119. 

^  Zuntz:  Verhandl.  der  physiol.  Ges.  zu  Beriin,  "Arch,  fiir  Physiol."  1893, 

P-378- 

°Lusk:  "Zeitschrift  fiir  Biologie,"  i8g8,  Bd.  xxxvi,  p.  in. 


72 


SCIENCE   OF   NUTRITION. 


Frentzel  ^  has  shown  the  effect  of  external  work  upon  the 
proteid  metabolism  of  fasting  dogs.  One  of  the  dogs  did  an 
amount  of  work  corresponding  to  216,937  kilogrammeters  in 
three  days.  The  proteid  metabolism  rose  during  the  work- 
ing hours  and  continued  high  on  the  fourth  day  which  was  one 
of  complete  rest  (possibly  the  premortal  rise  had  set  in).  Frent- 
zel computes  that  the  nitrogen  elimination  of  these  four  days 
(^20.7  grams)  represents  an  energy  equivalent  of  220,300  kilo- 
grammeters. This  could  not  cover  the  work  done  by  the  dog 
if  we  add  to  the  measured  work  that  which  was  done  by  the 
heart  and  respiratory  muscles.  The  proteid  metabolism  of  four 
days  is  therefore  entirely  insufficient  to  cover  the  work  done 
during  three.  The  source  of  the  energy  for  the  work  accom- 
plished must  therefore  be  found  in  an  increased  metabohsm  of 
fat.  The  increase  in  proteid  metabolism  above  that  of  rest 
was  not  sufficient  to  supply  7  per  cent,  of  the  energy  needed  to  do 
the  work.  The  record  of  the  dog's  nitrogen  metabolism  is  as 
follows : 


INFLUENCE  OF  WORK  ON  THE   N  METABOLISM    OF   FASTING 

DOGS. 


Day. 


I  St  to  4th 

5th 

6th 

7th 

8th 


9th 

loth 

nth 
i2th 


Work  or  Rest. 


Rest. 
Rest. 
Rest. 
Rest. 
Rest. 

Work. 


Work. 

Work. 
Rest. 


Food. 


100  g.  lard. 
100  g.     " 
100  g.     " 
Fasting. 


Grams  of  N  Excreted. 


Per  Day.  Per  Hour. 


3-'^3 
3-52 
3-71 
3-99 

4-97 
5.02 

5-63 
5.08 


0.1304 

0.1467 

0.1546 

0.1663 

*o.368o 

to.  1837 

/  *o.275o 

t  to. i960 

♦0.2400 

to.2335 

0.2117 


*Work.  t  Rest. 

Succi  did  not  show  a  similar  rise  of  proteid  metabolism 

'  Frentzel:  "Pfliiger's  Archiv,"  1897,  Bd.  Ixviii,  p.  212. 


STARVATION.  73 

from  the  effect  of  work.  The  eleventh  day  of  his  fast  he  spent 
in  bed.  On  the  twelfth  day  he  rode  a  horse  for  an  hour  and 
forty  minutes,  raced  for  eight  minutes  with  some  students,  and 
gave  an  exhibition  of  fencing  in  the  evening.  During 'the  day 
he  walked  19,900  steps.  The  urinary  nitrogen  on  the  eleventh 
day  (rest)  was  7.88  g. ;  on  the  twelfth  (work),  7.162;  and  on 
the  days  following  3.50,  5.33,  5-14,  5.05.  The  work  done  was 
evidently  at  the  expense  of  increased  metabohsm  of  fat.  That 
this  is  the  case  had  already  been  demonstrated  by  Pettenkofer 
and  Voit.^  A  fasting  man  at  work  showed  no  increase  in  his 
proteid  metabolism,  but  the  quantity  of  fat  burned  rose  enor- 
mously. This  is  shown  by  the  following  comparison  of  the 
number  of  grams  of  fat  burned : 

Day.  Night. 

Rest 116  g.  94  g. 

Work 312  g.  70  g- 

The  increase  of  fat  metabolism  during  the  day  is  two-and-a- 
half-fold  and  is  presumably  the  source  of  the  energy  for  the 
mechanical  work  accomplished.  During  the  night  following 
the  working  day  the  reduction  of  fat  combustion  as  compared 
with  the  night  before  is  due  to  more  profound  sleep. 

Another  phase  of  the  effect  of  work  is  shown  in  the  variation 
between  the  day  and  night  metabolism  of  Tigerstedt's  fasting 
medical  student,  J.  A.  The  average  carbon  dioxid  excretion  in 
grams  for  two-hour  periods  during  five  days  of  fasting  was  as 
follows.  The  figures  showing  the  elimination  during  the  hours 
of  sleep  are  printed  in  black  letters. 

A.  M.     p.  M. 

Time ..10-12     12-2     2-4      4-6      6-8     8-10  10-12 

Carbon  dioxid  (grams) -.54.8     57.2     54.1     57.8     59.5      66.4     46.5 

A.M. 

Time 12-2         2-4         4-6         6-8         

Carbon  dioxid  (gramsj 37.5       39.1       40.7       68.6 

^Pettenkofer  and  Voit:  "Zeitschrift  fiir  Biologie,"  1866,  Bd.  iii,  p.  459; 
C.Voit:  Ihid.,  Bd.  xiv,  1878,  p.  144. 


74 


SCIENCE   OF  NUTRITION. 


The  nitrogen  of  the  urine  was  also  less  during  sleep  than 
during  the  waking  hours : 


Fasting  Day. 


ist. 
2d. 

3d. 
4th 
5th 


NiN 

THE  Urine. 

Day. 

Night  (10  p.  M. 
to  10  A.M.) 

7. II 
6.87 
6.83 
7.91 
6.36 

4-93 
5-85 
6.65 

5-65 
4.98 

Johansson  ^  finds  that  the  inequahty  of  night  and  day  metab- 
oUsm  depends  on  muscular  work.  Sitting  up  raises  the 
metabohsm,  and  standing  does  so  still  more.  Even  when 
one  lies  in  bed,  restlessness  during  the  day  may  increase  the 
metabohsm.  And  when  perfect  muscular  relaxation  ensues 
there  may  still  be  influences,  such  as  light  on  the  retina  or  sounds, 
which  may  act  refiexly  on  the  organism  and  shghtly  increase 
the  metabohsm.  Johansson  illustrates  these  variations  in  the 
following  comparisons  between  night  and  day  excretion  of 
carbon  dioxid  of  starving  men,  the  night  CO  2  being  figured  at  100. 


Day  CO2. 


Complete  muscular  rest 

Ordinary  rest  in  bed 

Ordinar}'  life  (no  hard  work) . 


Author. 


Johansson. 
Johansson. 
Tigerstedt. 
Pettenkofer  and  Voit. 
Tigerstedt. 


Johansson  agrees  with  Tigerstedt  that  the  minimum  metab- 
olism of  a  man  in  bed  is  represented  by  24  to  25  calories  per 
kilogram  daily. 

The  temperature  of  the  fasting  organism  is  usually  normal. 
Luciani  found  a  normal  temperature  in  Succi  during  his  thirty- 
day  fast.  The  temperature  falls  only  a  few  days  before  death. 
Sonden  and  Tigerstedt'  find  that   the   diurnal  variations  per- 

'  Johansson:  "  Skandinav.  .\rchiv  fiir  Physiologie,"  1898,  Bd.  viii,  p.  109. 
*  Sonden  and  Tigerstedt:   Ibid.,  1895,  Bd.  vi,  p.  136. 


STARVATION. 


75 


sist  during  fasting  in  their  ordinary  rhythm.     The  average 
temperature  of  the  medical  student  J.  A.  during  his  five-day 


Crams  COi. 

per  hour 

00 


20 


ZS 


i<y 


15 


10 


27' 
Tenth 


jusi 


Aloon.. 


Sleep- 

Fig.  I. — Curve  of  carbon  dioxid  elimination  compared  with  Jurgensen's 
curve  of  normal  diurnal  temperature  variation.  This  individual  led  a  normal 
life  and  partook  of  his  usual  nourishment. 


fast  was  but  o.i6°  below  his  normal  temperature  when  food  was 
allowed  him.     These  diurnal  vaiations  are  exactlv  concomitant 


70  SCIENCE   OF  NUTRITION. 

with  the  fluctuations  of  carbon  dioxid  excretion  noted  on  a 
previous  page.  When  the  carbon  dioxid  production  increases, 
the  temperature  rises. 

This  parallelism  may  be  easily  shown  by  comparing  the  two 
factors  in  the  preceding  chart  as  given  by  Sonden  and  Tiger- 
stedt.*  Furthermore,  the  diurnal  variations  tend  to  disappear  if 
the  person  be  kept  in  a  state  of  muscular  rest,  and  the  day  and 
night  metabolisms  remain  the  same.  In  this  state  the  tempera- 
ture may  fall  0.6°  below  the  normal  on  account  of  the  absence  of 
muscle  movement.  This  regularity  of  temperature  and  metabo- 
lism is  beautifully  shown  in  the  following  chart  of  Johansson:^ 


Grams  CO  I 

Jgtrheur 


zo^. 


10  IZ 

Moon. 


31' 

Tetnfi 

3(>' 


J//^kt 


Fig.  2. — Carbon  dioxid  elimination  and  body  temperature  in  fasting  and  com- 
plete muscular  rest. 


'  Sonden  and  Tigerstedt:  Loc  cit.,  p.  132. 
^Johansson:  Loc.  cit.,  p.  142. 


STARVATION. 


/  / 


Inversion  of  the  normal  routine  of  life,  so  that  one  sleeps  in 
the  da)'time  and  is  awake  and  active  at  night,  brings  about  an 
inversion  of  curve  of  body  temperature.  This  is  well  sho^n 
in  the  monkey.^ 

'■  Goldbraith  and  Simpson:  Proceedings  of  the  Physiological  Society,  "Jour- 
nal of  Physiology,"  1903,  vol.  xxxiii,  p.  xx. 


CHAPTER  IV. 

THE  REGULATION  OF  TEMPERATURE. 

It  has  been  seen  that  the  temperature  of  a  warm-blooded 
animal  is  maintained  at  the  normal  throughout  a  fast.  Not 
only  this,  but  it  is  maintained  at  the  same  level,  even  though  the 
temperature  of  the  outside  environment  vary  from  o°  and  lower 
to  30°  to  35°.  In  cold-blooded  animals  the  temperature  of  the 
body  is  only  slightly  higher  than  that  of  their  environment  at 
the  time.  The  metaboHsm  of  such  animals  varies  with  the 
temperature.  The  frog  in  the  mud  during  the  winter  at  a 
temperature  of  4°  C.  has  quite  a  different  metaboHsm  from  that 
which  he  enjoys  during  the  summer  sunshine  as  he  sits  on  the 
river-bank  or  snaps  at  passing  flies.  The  curve  of  his  carbon 
dioxid  ehmination  at  various  temperatures  has  been  made  by 
E.  Voit  from  the  analyses  of  H.  Schultze,  and  is  given  below: 


COzmng 
frerfig.of 


0'      '      '      '  10'  '      '      ^~Io^ 

Fig.  3. — CO,  in  milligrams  per  hour  per  kg.  frog 


lemja. 


A  sudden  rise  in  the  frog's  metaboHsm  commences  at  about  20°. 
A  temperature  of  20°  corresponds  to  that  of  the  bear  and  marmot 

78 


THE    REGULATION    OF   TEMPERATURE.  79 

during  their  winter's  hibernation,  and  is  a  level  of  compara- 
tively low  metaboHsm.  This  reduction  in  activity  is  exem- 
pHfied  by  the  fact  that  a  cat  whose  temperature  has  been 
artificially  reduced  to  19°  may  have  but  one  heart-beat  per 
minute/ 

E.  Voit^  has  dra\vn  attention  to  the  fact  that  the  above  curv-e 
of  increasing  metabolism  with  increasing  temperature  corres- 
ponds to  the  increasing  abihty  of  the  frog's  muscle  to  contract, 
and  to  the  increasing  effectiveness  of  enzymotic  activity.  A 
warm  temperature  is  necessary  for  the  irritabihty  and  activity  of 
protoplasm.  The  warmth  of  the  sunshine  increases  the  irri- 
tabihty of  the  protoplasm  of  the  tree  in  the  spring,  with  the 
resulting  development  of  the  foHage.  Heat  is  not  the  cause  of 
the  metabohsm,  but  only  one  of  the  conditions  for  it.  In  warm- 
blooded animals  the  temperature  is  maintained  at  a  constant 
level  independent  of  chmatic  conditions,  and  this  level  is  a  favor- 
able one  for  the  activity  of  nerve  and  muscle.  It  would  indeed 
be  inconvenient  were  the  active  life  of  a  man  dependent  upon 
the  temperature  of  his  environment.  The  essential  mechanism 
for  the  regulation  of  the  body  temperature  is  through  the  nerves. 
The  action  of  cold  on  the  skin  may  stimulate  its  peripheral 
nerve-endings  which  are  sensitive  to  cold,  and  refiexly  effect  in 
the  organism  a  greater  heat  production,  and  a  vaso-constriction  of 
peripheral  blood-vessels :  the  action  of  heat,  on  the  contrary,  effects 
vasodilatation  and  production  of  sweat.  It  is  beheved  that  the 
cold-blooded  progenitors  of  warm-blooded  animals  changed 
their  habitat  from  the  sea  to  the  land  at  a  tropical  temperature 
which  is  at  present  possessed  by  their  descendants.  In  the 
course  of  development  these  animals  acquired  the  power  to 
maintain  that  ancestral  temperature,  which  proved  favorable 
for  the  activity  of  their  body  substance.  The  nervous  mechan- 
ism through  which  this  is  accomplished  is  twofold :  First,  there 
is  an  increased  production  of  heat  in  the  presence  of  external 

^  Simpson  and  Herring:  "Journal  of  Physiology,"  1905,  vol.  xxxii,  p.  305. 
^E.  Voit:   " Sitzungsber.     der    Ges.    fiir    Morph.    und    Physiol.,"    1896, 
Heft  in. 


8o  SCIENCE    OF   NUTRITION, 

cold  (the  chemical  regulation  oj  temperature),  and,  second,  there 
.is  a  variation  of  the  distribution  of  blood  on  the  surface  of 
the  body  in  order  to  modify  heat  loss  and  there  may  be  an  in- 
creased evaporation  of  water  from  the  body  (production  of 
sweat)  to  serve  the  same  purpose  (these  are  the  factors  of 
the  physical  regulation  oj  temperature) .  The  great  importance 
of  these  two  controlling  influences  will  be  seen  as  the  subject 
develops. 

If  the  body  were  a  mass  of  cells  having  the  shape  of  a  ball 
w^'th  a  constant  heat  production  in  its  center,  it  would  be  easy 
to  calculate  its  temperature  in  the  different  zones  of  the  interior. 
The  loss  of  heat  from  the  surface  would  obviously  be  equal  to 
the  heat  production,  if  the  temperature  of  the  ball  continued 
constant. 

If  two  balls  of  the  same  material,  but  of  unequal  size,  were 
equally  warmed,  the  smaller  would  cool  more  quickly  than  the 
larger  on  account  of  the  relatively  greater  exposed  surface  from 
which  heat  could  be  discharged.  The  heat  elimination  would 
be  proportional  to  the  surface  exposed. 

To  determine  the  surface  of  geometrically  similar  solids, 
and  hence  of  animals  of  similar  shapes,  the  following  formula 
was  used  by  Meeh*  in  which  S  =  surface  and  V  =  volume: 

_1_    ^    S£V 
Vf  V 

Since  animals  contain  the  same  materials,  one  may  sub- 
stitute W=  weight  for  V. 

Then  the  value  21i^  may  be  empirically  determined  for 

each  shape  or  animal,  and  this  value  =  k.     Hence  the  formula 
w^ould  read: 

=  k   or   S  =  k^w2 

The  value  of  k  or  the  constant  in  the  relationship  of  weight 
to  surface  in  each  animal  has  been  given  by  Rubner  as  follows: 

*  Meeh:  "Zeitschrift  fiir  Biologic,"  1879,  Bd.  xv,  p.  425. 


THE   REGULATION   OF  TEMPERATURE.  8l 

Man 12.3 

Dog 1 1. 2-10.3 

Rabbit 12. 9-12.0 

Rabbit  (without  ears) 10.8 

Calf 10.5 

Sheep 12. 1 

Cat 9.9 

Pig; 8.7 

Guinea-pig 8.5 

Fowl 10.4 

Rat 9.1 

White  mouse 11.4 

The  use  of  the  above  formula  rendered  possible  the  calcu- 
lation of  the  heat  elimination  per  unit  of  area  in  fasting  animals 
during  rest.  When  these  have  been  previously  weU  fed,  there 
is  a  surprising  uniformity  of  result.  It  is  Rubner's  law  that  the 
metaboHsm  is  proportional  to  the  superficial  area  of  an  animal. 
In  other  words,  the  metabolism  depends  on  the  amount  of  heat 
loss  at  the  surface,  and  its  variation  in  accordance  with  this  law 
is  necessary  for  the  maintenance  of  a  constant  temperature. 

Erwin  Voit^  has  calculated  the  following  general  table 
showing  the  heat  production  in  resting  animals  of  various  sizes 
at  medium  temperatures  of  the  environment : 


Weight  in  Kg. 

Horse 441 

Pig 128 

Man 64.3 

Dog 15.2 

Rabbit 2.3 

Goose 3.5 

Fowl 2.0 

Mouse  ^ 0.018 

Rabbit^  (without  ears) . .     2.3 

The  universality  of  this  law  of  Rubner's  is  remarkable. 
Even  at  a  room  temperature  of  30°  where  all  thermal  influence 
is  removed,  two  guinea-pigs  of  different  sizes  will  produce  heat  in 
proportion  to  their  surface.  In  this  case  there  is  a  minimum  of 
heat  production  determined  for  the  resting  organism  according 
to  the  law  of  superficial  area. 

^  E.  Voit:    "Zeitschrift  fiir  Biologic,"  1901,  Bd.  xli,  p.  120. 
^Rubner:  "Energiegesetze,"  1902,  p.  282. 
6 


Calories  Produced. 

Per  Kilo. 

Per  Sq.  M.  Surface. 

19. 1 

948 
1078 

32.1 

1042 

Si-S 
75-1 
66.7 

1039 
776 
969 

71.0 
212.0 

943 
1 188 

7S-I 

917 

82  SCIENCE    OF   NUTRITION. 

When  this  discovery  was  first  made,  the  interpretation  was 
offered  that  the  metabohsm  in  the  different  animals  was  in 
proportion  to  the  skin  area,  because  of  the  specific  sensory 
influences  of  cold  proceeding  from  a  definite  surface  (chemical 
regulation).  This  explanation  fell  when  Rubner  discovered 
that  at  a  temperature  of  30°,  under  which  condition  all  thermal 
stimulus  to  the  organism  ceased,  two  guinea-pigs  of  different 
sizes  still  produced  heat  in  proportion  to  their  skin  areas.  A 
similar  fact  was  noted  by  Frank  and  Voit^  who  found  that  the 
administration  of  curare,  which  paralyzes  the  voluntary  muscles, 
scarcely  affected  the  carbon  dioxid  output  of  a  dog  as  compared 
with  what  was  eliminated  during  ordinary  muscular  rest,  pro- 
vided the  temperature  of  the  animal  was  maintained  at  the 
normal  by  keeping  him  in  a  warmed  chamber.  The  mass  of 
living  cells  preserved  the  same  metabolism  as  before,  even 
though  a  pathway  of  heat  increase  had  been  cut  off  through 
paralysis  by  curare  of  the  motor  nerve-endings  in  the  muscles. 
Keeping  the  animal  in  a  warmed  chamber  was  necessary  in  this 
case,  for  Rohrig  and  Zuntz  -  had  sho^^^l  that  curarized  animals 
at  the  ordinary  room  temperature  lost  the  power  of  maintaining 
their  body  temperature  and  that  their  metabolism  decreased 
accordingly.  The  removal  of  the  chemical  regulation  caused 
a  behavior  toward  external  temperature  similar  to  that  in  cold- 
blooded animals. 

Although  the  effect  of  cold  on  the  skin  (inducing  chemical 
regulation)  was  of  itself  demonstrably  insufficient  to  account 
for  the  "law  of  skin  area,"  Rubner^  argues  that  even  at  30°  C, 
when  the  body  is  losing  heat  by  means  of  the  dilatation  of  the 
blood-vessels  and  the  evaporation  of  water  (physical  regulation), 
the  law  is  still  a  necessity  if  the  general  mechanism  for  loss  of 
heat  in  the  various  animals  is  the  same  in  all.  An  infant  pro- 
duces 90  calories  per  kilogram  in  twenty-four  hours,  an  adult 
32  calories.     Were  the  metabolism  of  an  adult  90  calories  per 

^  Frank  and  Voit:  "Zeitschrift  fur  Biologic,"  1901,  Bd.  xlii,  p.  309. 
*  Rohrig  and  Zuntz:  "Pfliiger's  Archiv,"  1871,  Bd.  iv,  p.  57. 
^Rubner:  "Energiegesetze,"  1902,  p.  174. 


THE  REGULATION  OF  TEMPERATURE.  83 

kilogram,  the  means  of  heat  eHmination  through  his  compara- 
tively smaller  surface  would  have  to  be  materially  modified 
if  a  normal  temperature  were  to  be  maintained  with  comfort. 

The  organism  therefore  preserves  the  tropical  temperature 
of  its  cells  at  the  expense  of  a  metabolism  which  is  proportional 
to  the  skin  area  of  the  individual. 

The  loss  of  heat  by  an  organism  is  by  the  following  paths: 

1.  Conduction  and  radiation. 

2.  Evaporation  of  water  from  lungs  and  skin. 

3.  Warming  the  food  ingested. 

4.  Warming  the  inspired  air  (conduction).  ■ 

The  great  outlets  for  heat  loss  are  by  conduction  and  radia- 
tion (of  which  in  the  dog  97.3  per  cent,  takes  place  through  the 
skin  and  2.7  per  cent,  through  the  lungs  ^)  and  through  the 
evaporation  of  water.  The  losses  through  warming  the  food, 
and  through  heat  of  solution  of  urinary  constituents,  through 
the  feces  and  the  warming  of  expired  carbon  dioxid  may  be 
ordinarily  disregarded. 

The  pathway  for  the  loss  of  heat  varies  with  the  temperature 
of  the  environment.  At  a  low  temperature  there  is  little  evapo- 
ration of  water,  and  at  a  temperature  of  37°  there  can  be  no  heat 
loss  by  radiation  and  conduction  (except  by  a  rise  in  body 
temperature)  and  water  evaporation  removes  the  whole  of  it. 
In  the  dog  at  a  high  temperature  there  is  distention  of  the  limbs 
to  promote  heat  loss  by  radiation  and  conduction,  and  rapid 
breathing  (polypnea)  with  extension  of  the  hyperemic  tongue 
to  promote  evaporation  of  water.  In  the  horse  and  in  man 
there  is  especially  an  outbreak  of  sweat,  which  is  not  possible 
in  the  dog  as  its  skin  does  not  secrete  sweat. 

It  has  been  seen  that  Lavoisier  noticed  that  cold  increased 
the  metabolism.  This  has  been  abundantly  confirmed.  The 
simplest  illustration  of  this  action  is  to  be  found  in  fasting  ani- 
mals. Rubner  has  called  this  increase  of  combustion,  and  there- 
fore of  heat  production,  the  chemical  regulation  of  the  body 
temperature.     It  is  the  same  as  burning  more  coal  in  the  fur- 

'  Rubner:  "Energiegesetze,"  1902,  p.  187. 


84 


SCIENCE   OF   NUTRITION, 


nace  on  a  cold  day  in  order  to  maintain  the  temperature  of  the 
house.  Voit  had  previously  demonstrated  this  action  in  the 
case  of  a  man  (see  below). 

Rubner  placed  a  fasting  guinea-pig  in  a  bell-jar  which  was 
ventilated  so  that  the  carbon  dioxid  production  could  be  deter- 
mined. The  temperature  of  the  bell-jar  could  be  changed  by 
immersing  it  in  water.     The  following  were  the  results: 

ACTION    OF    CHEMICAL    REGULATION    IN    THE    GUINEA-PIG. 


Temp,  of  Air. 


Temp,  of  Animal. 


Grams   of    COo   in 

I  Hr.  per  Kg. 

Animal. 


Percentage    Change 

of  CO2  FOR  Each   i" 

C.   Rise  in   Temp,  of 

Air. 


0.0 
II. 1 

20.8 
25-7' 
30-3 
34-9 
40.0 


37-0 
37-2 
37-4 
37-0 
37-7 
38.2 

39-5 


2.905 

2-151 
1.766 
1.540 
1-317 
1-273 
1-454 


—2-33 
—  1.84 
-2.67 

— 0.71 
+  2.82 


It  is  evident  from  the  table  that  there  was  a  constant  de- 
crease in  the  metaboHsm  as  the  air  was  warmed  from  0°  to  35° 
C.  The  metabohsm  at  0°  was  two  and  a  half  times  that  at  30°, 
an  increase  as  pronounced  as  is  incurred  as  the  result  of  severe 
muscular  work.  The  animal  at  0°  was  not  observed  to  move 
around  any  more  than  he  did  at  30°.  Other  experiments  con- 
firmed Rubner  in  the  view  that  the  critical  temperature,  or  the 
temperature  of  the  minimum  metaboHsm,  lay  at  t,t,°.  At  this 
point  temperature  had  the  least  influence  on  total  metabolism. 
When  the  temperature  is  raised  from  30°  there  is  at  first  no 
increase  in  the  metabolism.  This  is  due  to  the  action  of  the 
apparatus  for  the  physical  regulation  of  body  temperature. 
Accompanying  a  rising  temperature  the  blood-vessels  of  the  skin 
become  dilated  and  the  evaporation  of  water  from  the  body  is 
promoted.  These  factors  tend  to  maintain  the  normal  tempera- 
ture of  the  organism  by  physical  means.  If  the  temperature  of 
the  air  be  high,  so  that  the  physical  regulation  be  not  sufficient 
to  cool  the  body,  then  a  hypernormal  temperature  ensues.     Such 


THE    REGULATION    OF   TEMPERATURE. 


85 


a  febrile  temperature  raises  the  metabolism  by  warming  the 
cells,  as  was  seen  in  the  table  of  the  experiment  in  which 
the  guinea-pig  was  exposed  to  a  temperature  of  40°.  The  range 
of  the  physical  regulation — that  is,  the  period  during  which 
external  temperature  change  does  not  alter  metabohsm — de- 
pends, according  to  Rubner,  on  the  natural  protections  which 
an  animal  possesses  which  insure  him  against  heat  loss.  These 
are  two  in  number — the  hairy  covering,  and  the  thickness  of  the 
layer  of  subcutaneous  fat. 

Rubner  has  shown  that  the  hair  of  the  black  cat,  black  lamb, 
rabbit,  skunk,  raccoon,  mink,  musk-deer,  and  sheep  is  of  itself 
relatively  light  in  weight,  but  that  the  fur  contains  a  very  large 
quantity  of  air.  The  whole  of  the  fur  covering  of  these  animals 
consists  of  between  97.3  and  98.8  per  cent,  of  air.  The  fur 
therefore  really  consists  of  air  with  between  1.2  and  2.7  per  cent, 
of  hair.  The  shght  conductivity  of  the  fur  is  principally  de- 
pendent on  this  layer  of  stationary  air.  If  an  animal  be  covered 
with  a  fur  containing  this  stagnant  air,  he  will  be  better  protected 
from  loss  of  heat  than  if  he  had  none,  and  also  less  susceptible 
to  the  influence  of  cold  upon  the  surface  of  his  skin.  This  pro- 
tective covering  therefore  extends  the  range  of  the  physical 
regulation. 

Rubner^  gives  the  following  experiment  showing  the  in- 
fluence of  temperature  on  a  small  fasting  dog  with  long  hair: 


ACTION  OF  CHEMICAL  REGULATION  IN  THE  DOG. 


> 

< 
Q 

a: 

Z 

< 

H 
0 

< 

M 

a 

f=< 
0 

u 

g 

0 

u 

u 

< 

H 

0 

< 

fa 

s 
0 

cs 

u 

g 

S 
& 

0 
g 

< 

1 
§ 

< 
u 

i 

a 
0 
1-1 

< 

t 

0 
H 

(4 
« 

D 
H 
< 

a 

a 

td 

ist 

2d 

3d 

4th 

5th 

1.80 
1.56 
1.52 
1.56 
1.42 

0.06 
0.06 
0.06 
0.06 
0.06 

1.86 
1.62 
i-S8 
1.62 
1.48 

20.0 

22.4 
28.2 
18.9 

17-3 

I.I 

I.O 
I.O 

1.0 

0.9 

21.0 

23-4 
29.1 
19.9 
18.2 

14.9 
18.0 

23-9 
14-5 
13-7 

46.5 
40.4 

39-5 
40-5 
37-0 

183.6 
224.6 

294.7 
179.0 
169.3 

230.1 
264.6 
334-2 

219-5 
206.3 

20.0° 
15.2° 
7.6° 
30.0° 
25.2° 

^  Rubner:  "Die  Gesetze  des  Energieverbrauchs,"  1902,  p.  105. 


86 


SCIENCE   OF  NUTRITION. 


One  observation  was  made  in  this  experiment  on  the  dog 
which  was  not  possible  in  the  case  of  the  guinea-pig,  and  that 
concerned  the  nitrogen  excretion.  The  nitrogen  excretion  for 
twenty-four  hours  is  not  increased  by  exposing  the  dog  to  a  tem- 
perature of  7.6°.  The  increased  metabolism  is  entirely  at  the 
expense  of  fat.  We  have  seen  that  this  may  also  be  true  of 
work  which  may  be  accompHshed  at  the  expense  of  fat  without 
raising  the  proteid  metabohsm. 

Reduced  to  terms  of  calories  produced  per  kilogram  of  dog, 
the  following  results  are  obtained : 

Temperature.  Calories  per  Kilo. 

7.6° 86.4 

15.0° 63.0 

20.0° 55-9 

25-0° 54-2 

30.0° 56.2 

350° 68.5 

A  temperature  of  20°  was  readily  borne  by  this  dog  without 
any  increase  of  his  metabohsm.  The  period  of  no  chemical 
change  extended  over  at  least  ten  degrees  between  20°  and 
30°,  during  which  time  the  physical  regulation  alone  sufficed 
to  maintain  evenly  the  body's  temperature.  At  35°  a  decided 
increase  of  heat  production  set  in,  on  account  of  the  warming 
of  the  cells  through  insufficient  heat  loss.  That  the  range  of 
the  physical  regulation  of  the  temperature  of  this  small  dog  was 
due  to  his  long  hair  is  shown  by  the  change  in  his  metabohsm 
after  shaving  him.  Rubner  shows  this  in  the  following 
table : 


Temperature. 

Calories  per  Kilo. 

Normal  Coat  of  Hair. 

Shaved. 

20° 

55-9 
54.2 
50.2 

82.3 
61.2 
52.0 

25° 

30° 

THE  REGULATION  OF  TEMPERATURE.  87 

It  is  clearly  seen  that  this  dog  lost  his  power  of  physical 
regulation  between  20°  and  30°  as  soon  as  he  lost  his  covering 
of  hair.  His  metabolism  became  like  that  of  the  guinea-pig, 
increasing  with  a  reduction  of  temperature  from  30°  downward, 
an  illustration  of  chemical  regulation. 

E.  Voit^  shows  that  the  metabolism  of  a  pigeon  may  be 
doubled  after  removing  his  feathers. 

Babak  ^  finds  that  if  rabbits  are  shaved  and  varnished  with 
starch  paste  their  metabolism  rises  140  per  cent.,  which  in- 
crease maintains  their  body  temperature  at  the  normal  for 
several  weeks,  although  the  room  temperature  be  between  15° 
and  20°. 

To  determine  the  influence  of  the  second  factor,  that  of  the 
protecting  layer  of  fat,  Rubner^  investigated  the  influence  of 
temperature  on  the  metabolism  of  a  fasting  short-haired  dog, 
at  a  time  when  he  was  emaciated,  and  compared  it  with  the  fast- 
ing metabolism  after  the  same  dog  had  been  fattened.  The 
results  wTre  as  follows : 

Dog  (Thin).  Same  Dog  (Fat). 

Temperature.  Cal.  per  Kilo.  Temperature.  Cal.  per  Kilo. 

5-1° -121.3  7.3° - 120.5 

144° 100.9  15-5° - 83.0 

23.3° 70.7  22.0° - 67.0 

30.6° 62.0  31-0° 64.5 

It  appears  from  the  above  that  the  metabolism  of  the  dog 
was  the  same  at  a  low  temperature  in  both  cases,  but  that  the 
minimum  metabohsm  was  almost  reached  at  a  temperature  of 
22°  in  the  dog  when  he  had  a  protective  covering  of  fat,  which 
was  not  the  case  when  he  was  thin.  The  presence  of  adipose 
tissue,  therefore,  acts  in  the  same  way  as  does  a  warm  fur  to 
extend  the  range  of  the  physical  regulation,  and  to  delay  the 
onset  of  the  chemical  regulation  of  body  temperature. 

*Voit:    " Sitzungsber.   der    Ges.   fiir    Morph.  u.  Physiol.,"  1904.  Bd.  xix, 

P-  39- 

^  Babak:  "Pfliiger's  Archiv,"  1905,  Bd.  cviii,  p.  389. 
^Rubner:  Ibid.,  1902,  p.  137. 


88  SCIENCE   OF  NUTRITION. 

The  physical  regulation  may  be  increased  by  certain  volun- 
tary acts,  such  as  are  observed  when  a  dog  exposed  to  cold  lies 
down  and  curls  himself  up  in  such  a  way  as  to  offer  as  small  an 
exposed  surface  as  possible.  The  contrast  to  this  is  offered 
when  on  a  hot  day  the  dog  Ues  on  his  back  and  extends  his  limbs 
so  as  to  promote  the  loss  of  heat. 

Rubner^  compared  the  fasting  metabohsm  of  a  resting  dog 
exposed  to  air  at  about  i8°  with  that  of  the  same  dog  quietly 
resting  suspended  in  a  net,  by  which  means  his  surface  was 
more  exposed  to  the  influence  of  cold.  The  results  were  as 
follows : 

Day  of        Cal.  from         Cal.  from  ^-^^^^  Temp. 

Starvation.      Proteid.  Fat. 

Resting 2  33.79  430-9i  464-7  i7-5° 

Resting  in  net 3  33.79  S^i-So  615.2  18.2° 

Rubner^  also  cites  an  important  modification  of  metabohsm 
through  a  variation  in  the  humidity  of  the  atmosphere. 

At  a  medium  temperature  during  fasting  (as  well  as  on  a 
medium  diet)  the  metabohsm  of  a  dog  was  practically  unaffected 
by  an  increase  of  humidity  in  the  air,  as  appears  below : 

Cal.  in  Humidity  in 

Temperature  20.2°  24  Hours.  Per  Cent. 

Drv  day 258.4  34 

Humid  day 256.6  69 

More  on  dr\'  day 1.8 

However,  on  a  hberal  diet  the  metabohsm  increases  on  a  damp 
day  even  at  a  medium  temperature,  as  for  example : 

Cal.  in  Humidity  in 

Temperature  20.2"  2^  Hours.  Per  Cent. 

Verv  dry  day 249.4  13 

Humid  day. 261.9  66 

More  on  humid  day 12.5 

The  increase  is  5  per  cent. 

1  Rubner:  "Energiegesetze,"  1902,  p.  184. 
'  Rubner:  Ibid.,  1902,  p.  188. 


THE   REGULATION  OF  TEMPERATURE. 


89 


On  a  very  hot  day  (on  a  moderate  fat  diet)  the  dog's  metab- 
olism is  increased  by  the  presence  of  moisture  in  the  atmos- 
phere. 

Temperature  35°. 
Calories  per  Kg.  Humidity  in  Per  Cent. 


69.28 

73-54 


9.1 

50. o 


Under  these  circumstances  the  metabohsm  rose  6.1  per  cent,  in 
the  more  humid  air.  There  was  probably  an  overwarming  of 
the  cells,  on  account  of  the  difficulty  of  heat  loss  by  evaporation  of 
water.  A  cold  damp  climate  of  0°  to  5°  temperature  also  favors 
an  increased  metabohsm.  Rubner  attributes  this  action  of 
humidity  to  the  increased  conductivity  of  a  hair  covering  con- 
taining moisture,  and  says  that  this  loss  may  be  partially  bal- 
anced by  a  decreased  evaporation  of  water  from  the  lungs. 

The  metabohsm  and  the  manner  of  heat  loss  may  therefore 
be  variously  affected  by  the  condition  of  the  atmosphere  as  re- 
gards moisture. 

On  days  of  ordinary  dryness  Rubner  ^  calculates  the  follow- 
ing division  of  the  heat  loss  in  a  starving  dog  under  the  influence 
of  different  temperatures : 

INFLUENCE    OF   TEMPERATURE   ON  MANNER  OF  HEAT  LOSS. 


Temperature. 

Calories  Lost  by 

Conduction  and 

Radiation. 

Calories   Lost  by 

Evaporation  of 

Water. 

Total  Calories  of 
AIetabolism. 

Humidity 
IN  PER  Cent. 

7° 

78.5 
55-3 
45-3 
41. 

33-2 

7-9 

7.7 

10.6 

13.2 

23.0 

86.4 
63.0 

55.9 
54.2 
56.2 

24 
34 
29 

19 
14 

15° 

20° 

25° 

30° 

It  is  clear  that  at  7°  only  a  little  heat  is  lost  by  the  evaporation 
of  water  and  the  greater  part  by  conduction  and  radiation.  As 
the  surrounding  air  becomes  warmer  the  power  to  lose  heat  by 
radiation  and  conduction  diminishes  and  the  loss  through  the 
evaporation  of  water  increases. 

^Rubner:  "Energiegesetze,"  1902,  p.  189. 


90 


SCIENCE  OF  NUTRITION. 


Rubner  has  charted  this  experiment  after  making  allow- 
ances^ for  the  varying  moisture  conditions.  The  chart  is  here 
reproduced : 


Fig.  4. — Rubner's  chart  showing  the  manner  of  heat  loss  at  different  room 
temperatures  in  the  dog.  Blue,  Heat  loss  in  calories  through  evaporation  of 
water.     Red,    Heat  loss  in  calories  through  radiation  and  conduction. 

The  distance  between  opposite  points  of  the  curved  line  represents  the  total 
metabolism  at  a  particular  temperature. 

The  chart  epitomizes  the  method  of  heat  loss  in  a  starving  dog 
under  the  influence  of  varying  temperatures. 

The  discussion  of  the  metaboHsm  has  given  a  foundation  for 
the  understanding  of  the  basic  requirement  of  an  organism. 
The  minimum  requirement  for  energy  is  seen  to  be  present 
when  the  fasting  organism  is  surrounded  by  an  atmosphere 
having  a  temperature  of  30°  to  35°.     This  may  be  called  the 

*  Rubner:  "  Archiv  fiir  Hygiene,"  1891,  Bd.  xi,  p.  208. 


THE   REGULATION   OF   TEMPERATURE.  9 1 

basal  requirement,  the  minimum  of  energy  compatible  with  cell 
life.  This  basal  requirement  is  modified  by  temperature,  by 
food,  and  by  work,  and  it  is  an  important  factor  to  keep  in  mind 
(see  p.  177). 

The  principles  laid  down  here  regarding  the  lower  animals 
apply  equally  to  man.  He  too  may  come  under  the  influence 
of  chemical  regulation,  although  he  constantly  endeavors  to 
maintain  the  surface  of  his  skin  at  a  tropical  temperature  through 
the  use  of  clothes.  His  heat  loss  may,  like  the  dog's,  be  more 
difficult  if  he  be  covered  with  a  thick  layer  of  fat.  And  his 
metabolism  is  also  influenced  by  atmospheric  conditions  of 
moisture,  wind,  and  temperature. 

One  of  the  eariiest  demonstrations  of  the  action  of  chemical 
regulation  was  afforded  by  Voit,  who  placed  a  fasting  man 
weighing  70  kilograms  in  the  Pettenkofer-Voit  respiration  ap- 
paratus and  determined  the  carbon  dioxid  and  nitrogen  output 
for  six  hours.  The  person  accustomed  himself  to  the  given 
temperature  by  staying  under  its  influence  for  some  time  previous 
to  the  commencement  of  the  experiment.  In  the  cold  experi- 
ments the  ventilating  air  was  derived  from  the  winter  atmos- 
phere. On  the  very  warm  days  the  air  was  artificially  heated. 
Voit  ^  gives  the  following  results: 

EFFECT  OF   TEMPERATURE  ON  THE  METABOLISM  OF  A 
FASTING  MAN. 
Temperature.  CO 2  Excreted  in  G.        N  in  Urine  in  G. 

4-4° 210.7  4-23 

6.5° 206.0  4.05 

9.0° 192.0  4.20 

14-3° I55-I  3-8i 

16.2° 158.3  4.00 

23-7° 164.8  3.40 

24.2° 166.5  3.34 

26.7° 160.0  3.97 

30.0° 1 70.6  ... 

The  nitrogen  elimination  remains  unaffected  by  temperature. 
At  the  ordinary  room  temperature  there  scarcely  seems  to  be 
any  increase  in  carbon  dioxid  output,  but  at  the  lower  temper- 
atures the  quantity  of  the  fat  metabohsm  is  markedly  increased, 

*  Voit:  "Zeitschrift  fiir  Biologie,"  1878,  Bd.  xiv,  p.  80  . 


92  SCIENCE   OF   NUTRITION. 

as  shown  by  the  rise  of  carbon  dioxid  eHmination.  The  in- 
dividual sat  quietly  in  a  chair,  but  at  a  temperature  of  4.4" 
could  not  prevent  himself  from  shivering. 

The  whole  effect  of  the  chemical  regulation  in  man  has  been 
attributed  by  Johansson^  to  the  additional  metaboUsm  due  to 
shivering.  Voit  did  not  believe  that  this  could  be  the  cause, 
nor  that  the  increased  respiratory  activity  could  account  for  the 
rise  in  metabolism.  Voit  beheved  the  increase  to  be  a  reflex 
stimulus  of  cold  on  the  skin  which  raised  the  power  of  the 
muscle  cells  to  metaboHze.  Voit's  views  have  been  confirmed  in 
Rubner's  laboratory-  in  the  following  series  of  experiments  on 
a  man: 

Temperature.  CO2  in  Grams  per  Hour. 

15° 323 

20° 300 

23° 27.9 

25° 31-7 

29° 32-4 

In  this  experiment  there  was  no  shivering  at  a  temperature 
of  15°  and  yet  the  metaboHsm  increased  from  what  it  was  at 

23°. 

It  has  also  been  shown  that  cool  baths  and  winds  increase 
the  metabolism,  which  must  be  effected  through  the  chemical 
regulation.  Lefevre^  states  that  a  man,  who  has  been  inured 
to  it,  may  sit  naked  for  several  hours  in  a  cold  wind  without  loss 
of  body  temperature. 

Rubner^  has  measured  the  effect  of  baths  and  douches  last- 
ing three  and  a  half  to  five  minutes.  When  the  water  has  a  tem- 
perature of  16°  he  finds  that  the  carbon  dioxid  elimination  may 
be  very  largely  increased,  especially  in  the  case  of  the  douche. 
The  effect  of  the  douche  was  more  marked  if  taken  before 
breakfast  when  the  intestinal  tract  is  free  from  food.  The 
results  before  breakfast  were  as  follows: 

'  Johansson:  "Skan.  Archiv.  fiir  Physiologic,"  1896,  Bd.  vii,  p.  123. 

^  Rubner:  "Energiegesetze  "  1902,  p.  203. 

^  Lefevre:  "Comptes  rendus,"  1894,  p.  604. 

*  Rubner:  "Archiv  fiir  Hygiene,"  1903,  Bd.  xlvi,  p.  390. 


THE    REGULATION    OF   TEMPERATURE.  93 

INFLUENCE  OF  COLD  BATHS  ON  METABOLISM  IN  MAN. 


Douche    16°.      In- 
crease IN  PER  Cent. 


Bath  16°.  Increase 
IN  PER  Cent. 


Volume  of  respiration  . , 
Carbon  dioxid  excreted 
Oxygen  absorbed 


54-5 
149-5 
no. I 


22.9 
64.8 
46.8 


A  cold  bath,  especially  a  douche,  will  therefore  stimulate  to  a 
greatly  increased  metabolism.  The  respiratory  quotient  indicates 
that  the  increased  metabohsm  is  at  the  expense  of  the  glycogen 
supply.  There  is  an  after-effect  which  lasts  about  one  and  a  half 
hours,  indicating  an  increased  metabolism  during  that  time. 
This  may  be  the  expression  of  the  body's  attempt  to  maintain  a 
normal  temperature  after  being  somewhat  cooled  (see  also  p.  254). 

It  is  obvious  that  a  cold  bath  will  be  liable  to  induce  shiver- 
ing unless  by  mechanical  effort,  such  as  swimming,  the 
metabohsm  is  increased  so  as  to  supply  calorific  energy  in 
another  way  than  through  chemical  regulation. 

A  bath  of  35°  has  no  effect  on  metabolism. 

Rubner  finds  that  a  bath  at  44°  again  increases  the  metabo- 
lism, the  increase  being,  for  the  volume  of  respiration,  18.8  per 
cent.,  for  carbon  dioxid  32.1  per  cent.,  and  for  oxygen  17.3  per 
cent.  This  is  probably  due  to  the  overwarming  of  the  cells. 
Baths  at  this  temperature  find  favor  among  the  Japanese. 

The  effect  of  wind  is  such  that  an  imperceptible  air  current 
may  have  a  very  pronounced  effect.  Rubner  ^  has  shovm  that 
wind  becomes  perceptible  when  it  attains  a  velocity  of  0.4  to 
0.5  meter  a  second,  and  that  if  a  wind  much  below  this  threshold 
value,  having  a  velocity  of  0.18  meter  per  second,  act  upon  the 
exposed  area  of  the  arm,  there  is  an  increased  heat  loss  of  be- 
tween 19  and  75  per  cent.,  depending  on  the  temperature  of  the 
wind,  above  what  would  be  lost  were  the  air  quiet. 

The  effect  of  wind  of  moderate  humidity  and  different  tem- 
peratures on  the  metabolism  of  a  man  clad  in  summer  clothes, 
as  compared  with  the  metabolism  during  atmospheric  calm,  is 
shown  in  Wolpert's  ^  experiment  below: 

'  Rubner:  "Archivfiir  Hygiene,"  1904,  Bd.  1,  p.  296. 
^Wolpert:  Ihid.,  1898,  Bd.  xxxiii,  p.  206. 


94 


SCIENCE    OF   NUTRITION. 


INFLUENCE  OF  WIND  ON  METABOLISM  IN  MAN. 


Temperature. 


Calm. 


'Wind  i  Meter  per   [  Wind  8  Meters  per 
Second.  i  Second. 


Grams     COj     per    Gpims     COj     per 
Hour.  I  Hour. 


Grams      CO2 
Hour. 


According  to  this  a  breeze  having  a  temperature  of  15-20°  and 
moving  at  the  rate  of  about  15  miles  per  hour  (8  meters  per 
second)  has  a  greater  effect  upon  the  metabohsm  of  a  man  clad 
in  summer  clothing  than  a  temperature  of  2°  would  have  during 
perfect  atmospheric  quiet.  In  all  the  experiments  the  smallest 
amount  of  carbon  dioxid  is  eliminated  between  30°  and  40°. 

The  above  experiments  were  performed  on  a  thin  man,  and 
it  will  be  noticed  that  there  was  no  rise  in  his  metabolism  at  a 
temperature  of  between  35°  and  40°.  Rubner  explains  this  as 
due  to  the  sufficiency  of  the  evaporation  of  perspiration  on  the 
surface  for  the  cooling  of  the  organism. 

A  fat  man,  however,  with  a  thick,  ill- conducting  layer  of 
adipose  tissue,  is  not  so  immune  to  the  effect  of  high  tempera- 
tures upon  his  metabolism.  This  is  especially  pronounced  in 
a  damp  chmate.  Thus  Rubner^  obtains  the  following  results 
from  a  fat  man  wcarins;  clothes: 


INFLUENCE  OF  TEMPERATURE  .\ND  HUMIDITY  ON  THE  ME- 
TABOLISM OF  A  FAT  M.\N. 


20"... 
28-30= 

36-37' 


Humidity  30  per  cent. 


Humidity  60  per  cent. 


Temperature.  ,  qq^   j^    grams  I  HoO  eraporated  '  CO2   in    grams  ]  H2O  evaporated 

per  hour.       1        per  hour.  per  hour.        1        per  hour. 


33-7 
36.9I 


42.6' 


30-7 
44-5' 


46.7* 


17 

170-f 

31  g- 
sweat. 
186 

1-255  g- 
sweat. 


3  Body  temjjerature  rose  0.4° 

4  "  "  "     0.9° 


1  Body  temperature  rose  0.1° 

2  "  "  "      0.0° 

*  Rubner:  "  Energiegesetze,"  1902,  pp.  208,  232 


THE    REGULATION    OF    TE1IPEILA.TURE.  95 

The  fact  that  in  the  experiment  where  there  was  30  per  cent, 
humidity  the  metabohsm  largely  increased  at  36-37°  without 
concomitant  rise  in  body  temperature,  leads  Rubner  to  theorize 
that  there  must  have  been  an  overheating  of  the  cells  where  the 
metabohsm  was  progressing,  even  though  this  might  not  have 
been  determinable  by  the  clinical  thermometer. 

It  appears  that  on  a  hot,  humid  day  the  metabohsm  of  a  fat 
individual  may  be  fifty  per  cent,  higher  than  on  a  day  of  moder- 
ate temperature  and  the  same  humidity.  The  whole  of  the 
body  heat  is  lost  through  the  evaporation  of  water  which  is  here 
hindered  by  the  humidity;  and  besides,  there  is  a  large  excre- 
tion of  sweat  which  is  always  accompanied  by  a  feehng  of  phys- 
ical exhaustion.  At  a  moderate  temperature,  where  the  greater 
part  of  the  heat  loss  is  by  radiation  and  conduction,  the  ex- 
cretion of  water  is  not  excessive. 

There  can  be  no  doubt  that  climatic  conditions  modify 
racial  characteristics.  The  emigrant  from  Northern  Europe, 
livinguponafarm  in  the  hot  and  often  moist  chmate  of  an  Ameri- 
can summer,  must  restrict  his  layer  of  adipose  tissue  if  he  is  to 
live  comfortably.  The  same  holds  true  in  Italy.  The  difference 
between  John  Bull  and  Uncle  Sam  seems  to  be  one  of  chmatic 
adaptation  On  the  contrary,  the  Eskimo  cultivates  a  thick,  fat 
layer  to  protect  himself  from  frost.  It  is  also  interesting  to  note 
that  prostrations  from  the  heat  appear  in  New  York  with  66 
per  cent,  humidity  and  a  temperature  of  31.5°  (2.30  p.m., 
August  24,  1905).  Rubner^  says  that  a  hghtly  clad  thin  man, 
at  a  temperature  of  30°  with  humidity  at  65  per  cent.,  bore  the 
effect  so  badly  that  he  feared  to  raise  the  temperature  to  35°. 
This  individual  had  readily  tolerated  35°  in  dry  air. 

The  maximum  mortality  from  "summer  troubles"  in  chil- 
dren in  New  York  coincides  with  the  first  great  wave  of  heat 
accompanied  by  humidity  which  falls  upon  the  city.  Similar  cli- 
matic conditions  at  later  dates  are  not  so  fatal.  It  may  be 
that  the  fatahty  of  these  intestinal  affections  is  due  to  the  inef- 
ficiency of  the  apparatus  for  the  physical  discharge  of  heat  in 

^  Rubner:  "Energiegesetze,"  1902,  p.  232. 


96 


SCIENCE   OF   NUTRITION. 


the  infant  organism.     It  is  also  possible  that  infection  may  be 
more  readily  achieved  under  these  conditions  (p.  183). 

Another  factor  in  the  heat  regulation  of  man  is  clothes. 
Certain  savage  races  do  without  clothes,  as,  for  example,  na- 
tives of  Terra  del  Fuego,  who  substitute  a  covering  of  oil.  In 
such  races  the  process  of  "hardening"  or  the  development  of 
the  physical  regulation  must  be  carried  to  a  maximum.  In 
civilized  countries  man  endeavors  to  remove  all  the  influence 
of  chemical  regulation  by  keeping  his  skin  covered.  Only  about 
20  per  cent,  of  his  surface  is  normally  exposed  to  the  air.  The 
most  important  constituent  of  clothes  is  the  air,  which  is  a  much 
worse  conductor  of  heat  than  is  the  fiber.  This  is  especially 
true  of  furs  (p.  85).  Thickness  of  the  cloth  will  give  a  greater 
layer  of  air  and  will  prevent  heat  loss  from  the  body.  A  densely 
woven  cloth  prevents  proper  ventilation  and  does  not  absorb 
moisture.  In  hot  weather  a  porous  cloth  next  to  the  skin  which 
can  absorb  moisture  and  permit  its  ready  evaporation  is  of  high 
importance.  If  such  a  garment  become  thoroughly  wet  the 
evaporation  of  sweat  at  a  high  temperature  is  largely  prevented, 
to  the  great  discomfort  of  the  individual,  while  at  a  lower  tem- 
perature heat  loss  through  conduction  is  greatly  facilitated,  with 
a  sensation  of  chill.  Two  experiments  cited  by  Rubner^  in- 
dicate the  effect  of  clothes  on  metabolism.  An  individual  was 
kept  at  a  temperature  of  between  11  and  12°  and  wore  different 
clothes  at  different  times.  His  carbon  dioxid  and  water  ex- 
cretion were  as  follows: 

INFLUENCE  OF  CLOTHES  ON  METABOLISM  IN  MAN  AT  A  TEM- 
PERATURE OF  11-12°. 


Summer  clothes 


Summer  clothes  and  win- 
ter overcoat 

Summer  clothes  and  fur 
coat 


CO2  IN  Grams  per 
Hour. 


28.4 

26.9 
23.6 


H2O  IN  Grams  per 
Hour. 


58 
63 


Remarks. 


Cold,  occasional 

shivering. 
Chilly  part  of  the 

time. 

Comfortably 

warm. 


'  Rubner:  "Energiegesetze,"  1902,  p.  225. 


THE  REGULATION  OF  TEMPERATURE.  97 

When  the  man  was  comfortable  the  chemical  regulation  of  tem- 
perature was  ehminated. 

Rubner  points  out  that  while  the  radiant  energy  of  the  sun 
is  large  in  quantity,  he  has  been  unable  to  find  any  influence 
upon  a  man  under  ordinary  circumstances,  but*believes  that  it 
may  take  the  place  of  heat  produced  through  chemical  regulation 
on  cold  days.  Thus  a  person  living  in  the  high  altitude  of  Davos, 
Switzerland,  feels  much  more  comfortable  in  the  sun  on  a  cold 
day  than  he  does  in  the  shade.  However,  Zuntz  while  living 
on  the  summit  of  Monte  Rosa  found  that  sunlight  did  not 
reduce  metabolism  (p.  218). 

In  what  follows  it  will  be  shown  that  the  ingestion  of  food 
may  add  to  the  heat  production  of  the  organism  and  diminish 
the  necessity  of  heat  production  through  chemical  regulation  in 
cold  weather.  Also,  it  may  very  uncomfortably  increase  the  pro- 
duction of  heat  and  perspiration  in  warm  weather,  especially 
if  proteid  be  largely  taken  (p.  183). 

From  this  chapter  the  influence  of  climate  is  seen  to  be  note- 
worthy. It  explains  why  a  temperature  of  —40°  may  be  com- 
fortably borne  in  winter,  in  the  Adirondacks,  for  example,  if 
the  air  be  dry  and  still;  how  a  much  warmer  atmosphere  which 
is  damp  and  windy  may  "cut  to  the  bone"  with  cold;  how  a 
hot,  dry  climate  may  be  entirely  comfortable,  when  air  at  the 
same  temperature  laden  with  moisture  may  strike  dowTi  many 
fatally  and  oppress  every  one;  and  how  the  effect  of  heat  may 
be  modified  by  the  breezes  and  baths  at  the  seashore. 

It  does  not  explain  the  effect  of  the  dry  sirocco  wind  which 
blows  from  the  Desert  of  Sahara,  the  universal  depressant  action 
of  which  has  been  attributed  to  unknown  cosmic  influences. 


CHAPTER  V. 
THE  INFLUENCE  OF  PROTEID  FOOD. 

It  has  been  thought  that  proteid  was  a  food  which  was  in 
itself  sufficient  for  all  the  requirements  of  the  body.  Pfliiger^ 
was  able  to  keep  a  very  thin  dog  in  good  condition  and  doing 
active  exercise  during  a  period  of  seven  months,  the  sole  diet 
being  meat  cut  as  free  from  fat  as  possible,  Pfliiger  says  that 
the  fat  and  glycogen  content  of  the  meat  ingested  could  not  have 
yielded  sufficient  energy  to  provide  for  the  action  of  the  heart 
alone.  It  must  be  remembered,  however,  that  meat  is  not  pure 
proteid  but  is  mixed  with  salts  and  water.  The  simplest  diet 
capable  of  maintaining  the  body  in  condition  is  therefore  a  mix- 
ture of  materials,  or  foodstuffs.  Such  a  mixture  of  foodstuffs 
is  called  a  food.  A  foodstuff  is  a  material  capable  of  being 
added  to  the  body's  substance,  or  one  which  when  absorbed  into 
the  blood-stream  will  prevent  or  reduce  the  wasting  of  a  neces- 
sary constituent  of  the  organism. 

The  foodstuffs  are: 

Proteids. 

Gelatinoids. 

Carbohydrates. 

Fats. 

Sahs. 

Water. 

A  food  is  a  palatable  mixture  of  foodstuffs  which  is  capable 
of  maintaining  the  body  in  an  equiUbrium  of  substance,  or  ca- 
pable of  bringing  it  to  a  desired  condition  of  substance.  The 
ideal  food  is  a  palatable  mixture  of  foodstuffs  arranged  together 

'Pfluger:  "Pfliiger's  Archiv,"  1891,  Bd.  1,  p.  98. 


THE   INFLUENCE    OF   PROTEID    FOOD.  99 

in  such  proportion  as  to  burden  the  organism  with  a  minimum  of 
labor.     These  definitions  are  Voit's/ 

When  proteid  alone  is  ingested  by  a  normal  adult  it  is  very 
readily  burned,  and  is  only  with  the  greatest  difficulty  deposited 
so  as  to  form  new  tissue  in  the  organism. 

In  the  early  experiments  of  Bischoff  and  Voit,  the  fact  is 
recorded  that  a  dog  weighing  35  kilograms  may  excrete  12 
grams  of  urea  in  twenty-four  hours,  and  the  same  dog  after 
receiving  2500  grams  of  meat  may  excrete  184  grams,  fifteen 
times  as  much. 

Voit^  has  shown  that  if  that  quantity  of  meat  be  admin- 
istered which  corresponds  to  what  is  burned  in  starvation, 
nitrogen  equihbrium  will  not  be  established,  but  some  of  the 
body's  flesh  will  also  be  metabohzed.  This  latter  quantity 
grows  steadily  less  if  the  amount  of  meat  ingested  be  gradually 
increased  until  finally  the  point  of  nitrogen  equilibrium  is  reached, 
at  which  the  amount  of  meat  ingested  is  equal  to  that  destroyed 
in  the  body.  To  illustrate  this  Voit  gives  the  following  table, 
the  results  of  work  done  on  a  dog : 

Change  in 
THE  Body. 

—233 
— 190 

—79 
-65 
—41 

-I-20 
+  54 

Nitrogen  equilibrium  was  not  reached  until  1200  grams  of  meat  were  given, 
or  about  five  times  the  amount  of  the  fasting  proteid  metabolism. 

The  above  experiments  were  made  in  1858.  It  is  no  longer 
customary  to  calculate  the  proteid  metabolism  in  terms  of  flesh 
destroyed,  but  in  terms  of  nitrogen.  The  old-fashioned  term 
flesh  meant  meat  with  a  nitrogen  content  of  3.4  per  cent.  It 
served  to  illuminate  the  significance  of  metaboHsm  at  a  time  when 
few  were  instructed  in  this  field  of  work. 

E.  Voit  and  Korkunofl^  have  pubhshed  a  research  of  sim- 

^  Voit:  Hermann's  Handbuch,  "Stoflwechsel,"  1881,  pp.  330,  344. 

2  Voit:  Ibid.,  1881,  p.  106. 

^  E.  Voit  and  Korkunoff:  "Zeitschrift  fur  Biologie, "  1895,  Bd.  xxxii,  p.  58. 


Meat 

Flesh 

Administered. 

Destroyed. 

0 

233 

0 

190 

300 

379 

600 

665 

900 

941 

1200 

1 180 

1500 

1446 

lOO  SCIENCE    OF    NUTRITION. 

ilar  character.  They  fed  a  dog  with  meat  which  had  been  treated 
with  lukewarm  water  to  remove  the  extractives,  and  which  was 
then  squeezed  in  a  press.  This  process  removes  most  of  the 
nitrogen  containing  substances  other  than  proteid.  A  dog  will 
readily  eat  this  washed  meat  or  "proteid."  The  idea  was  to 
determine  the  minimum  quantity  of  proteid  which  it  was  pos- 
sible to  ingest  and  still  maintain  nitrogen  equilibrium.  The 
different  quantities  of  meat  tabulated  below  were  given  con- 
tinuously for  two  or  three  days  at  a  time.  Only  the  results  of 
the  last  day  of  each  of  these  periods  are  quoted : 

Food.  N  in  Food.        N  in  Excreta.         Difference. 

Stan-ation o  3-996  — 3-996 

loo  g.  meat 4.10  5-558  — 1.458 


140  g. 
165  g- 
185  g- 
200  g. 

230  g- 
360  g. 
410  g, 
360  g. 


5.74  6.495  — 0-7S5 

6.77  7.217  —0.447 

7.59  7.804  —0.214 

8.20  8.726  — 0.526 

.10.24  10.579  -^-339 

.11.99  12.052  - — 0.062 

15-58  14-314  -l-r.266 

13. 68  13.622  +0.05S 


Starvation,  third  day 4.026  • — 4.026 

The  figures  show^  that  nitrogen  equilibrium  was  reached 
only  after  supplying  three  and  a  half  times  the  amount  of  proteid 
metabolized  in  starvation.  The  authors  calculate  that  at  this 
time  of  nitrogen  equilibrium  the  dog  was  still  losing  28  grams 
of  body  fat,  and  that'  not  much  more  than  fifty  per  cent,  of  the 
total  energy  hberated  in  the  organism  was  furnished  by  the  pro- 
teid metabolism  of  the  time.  One  may  thus  have  nitrogen 
equiUbrium  without  having  carbon  equihbrium. 

Systems  of  diet  for  fat  people  arc  based  on  this  knowledge. 
A  loss  of  proteid  is  highly  undesirable,  while  a  gradual  loss  of 
adipose  tissue  may  be  a  great  relief  to  the  obese. 

Bornstein*  finds  that  he  can  add  proteid  to  his  body  and 
burn  his  body  fat  on  a  mixed  diet  containing  1600  calories 
with  118  grams  of  proteid.  Such  a  diet  contained  a  fuel  value 
less  than  the  requirement  of  his  organism  (p.  157). 

If  the  quantity  of  meat  ingested  be  steadily  increased  after 

'  Bornstein:  "Berliner  klinische  Wochenschrift,"  1904,  Xo.  46. 


THE  INFLUENCE  OF  PROTEID  FOOD. 


lOI 


nitrogenous  equilibrium  has  been  reached,  the  proteid  metabo- 
hsm  will  gradually  increase,  nitrogenous  equihbrium  will  be 
established  at  higher  and  higher  levels,  and  there  will  be  a  cor- 
responding diminution  in  the  amount  of  fat  burned.  This  was 
shown  in  the  following  experiment  of  Voit,^  who  gave  different 
quantities  of  meat  to  a  large  dog  weighing  30  kilograms. 

INFLUENCE  OF  INGESTING  INCREASING  QUANTITIES  OF  MEAT. 

Weights  are  in  Grams. 


Meat  Ingested. 

Flesh 
Destroyed. 

Gain  or  Loss  of 
Body  Flesh. 

Gain   or  Loss 
of  Body  Fat. 

Respiratory 
Quotient. 

0 

500 

1000 

1500 

1800 

2000 

2500 

165 

599 

1079 

1500 

1757 
2044 
2512 

-165 

—99 

—79 

0 

+  43 
—44 
— 12 

^5 
—47 
—19 

+  4 

+  1 

+  58 

+  57 

.72 
.76 

•74 
.81 

.84 

Nitrogen  equilibrium  existed  after  the  ingestion  of  1500  grams 
of  meat  and  there  was  also  no  loss  of  body  fat  (carbon  equilib- 
rium). When  2000  grams  and  even  2500  grams  of  meat  were 
supphed  it  was  all  destroyed,  as  was  indicated  by  the  amount  of 
nitrogen  in  the  urine,  but  a  certain  quantity  of  carbon  belonging 
to  the  ingested  proteid  was  not .  eliminated  in  the  respiration 
but  was  retained  in  the  body.  This  carbon  Pettenkofer  and 
Voit  believed  to  have  been  laid  up  in  the  body  in  the  form 
of  fat. 

The  respiratory  quotient  in  the  foregoing  series  gradually 
rises  as  would  be  expected  from  the  increasing  prominence 
of  the  proteid  in  the  metabolism  (p.  27).  Meat  alone  will 
therefore  support  a  dog.  Rubner^  says  that  a  man  cannot  live 
on  meat  alone,  not  because  the  intestinal  canal  cannot  digest  it, 
but  because  of  the  physical  Hmitations  of  the  apparatus  of  mas- 
tication. 


^  Voit:  "Stoffwechsel,"  1881,  p.  117. 

^  Rubner:Leyden's"Handbuch  derErnahningstherapie,"  1903,  Bd.i,  p.  42. 


I02  SCIENCE    OF   NUTRITION. 

A  subject  of  interest  akin  to  the  value  of  proteid  in  metabo- 
lism is  that  of  the  value  of  gelatin.  Gelatin  is  a  substance  which 
contains  very  nearly  the  same  quantity  of  nitrogen  as  proteid; 
it  breaks  up  on  chemical  treatment  into  the  same  amino  acids, 
except  that  it  does  not  yield  tyrosin,  cystein  and  tryptophan. 
In  the  diabetic,  gelatin  yields  the  same  amount  of  sugar  as  does 
proteid.'  To  what  extent  gelatin  may  take  the  place  of  pro- 
teid in  the  body's  metabolism  has  long  been  the  subject  of 
inquiry. 

It  was  shown  first  by  Bischoflf  and  Voit "  that  no  matter  how 
much  gelatin  was  ingested  it  was  always  completely  burned  and 
some  of  the  body's  proteid  in  addition.  Therefore  gelatin  never 
builds  up  new  tissue,  although  it  may  somewhat  diminish  tissue 
waste.  Gelatin  may  be  formed  from  proteid  in  the  body,  but 
it  cannot  be  reconverted  into  proteid  nor  act  like  proteid  in 
metabolism.  Kirchmann,^  working  in  the  laboratory  of  Erwin 
Voit,  has  shown  to  what  extent  gelatin  spares  proteid  in  metabo- 
lism. If  one  takes  the  amount  of  proteid  metabolism  in  starva- 
tion as  one,  then  the  ingestion  of  about  the  same  quantity  of 
gelatin  reduces  the  body's  proteid  waste  23  per  cent.,  and  if 
eight  times  this  amount  of  gelatin  be  given  the  tissue  waste  may 
be  reduced  35  per  cent.  In  other  w^ords,  the  ingestion  of  7.5 
per  cent,  of  the  total  heat  requirement  of  the  organism  in  the 
form  of  gelatin  spares  23  per  cent,  of  the  body's  proteid,  while 
the  ingestion  of  60  per  cent,  of  the  requirement  will  only  cause 
a  decrease  of  35  per  cent,  in  proteid  waste.  Krummacher  * 
showed  that  the  ingestion  of  the  full  heat  requirement  of  the 
animal  in  the  form  of  gelatin  reduced  the  fasting  proteid  metab- 
olism by  only  37.5  per  cent.  It  is  evident  that  no  matter  how 
much  gelatin  be  given,  tissue  proteid  continues  to  be  destroyed, 
and  it  is  also  evident  that  a  small  quantity  of  gelatin  has  almost 
as  great  an  effect  as  a  large  quantity. 

^  Reilly,  Nolan,  and  Lusk:  "American  Journal  of  Physiology,"  1898,  vol.  i, 
P-  395- 

^  Voit:  Hermann's  Handbuch,  "Stoffwechsel,"  1881,  p.  396. 
^  Kirchmann:  "Zeitschrift  fur  Biologie,"  1900,  Bd.  xl,  p.  54. 
*  Krummacher:  Ibid.,  1901,  Bd.  xlii,  p.  242. 


THE   INFLUENCE   OF  PROTEID   FOOD.  I03 

An  extremely  interesting  experiment  of  Kauffmann^  shows 
that  when  the  lacking  tyrosin,  cystein,  and  tryptophan  are  mixed 
with  gelatin  in  the  proportions  in  which  they  occur  in  true  pro- 
teid,  and  are  given  to  a  dog  or  to  a  man,  nitrogen  equilibrium 
may  be  estabhshed. 

In  recent  years  the  idea  has  been  gaining  ground  that  pro- 
teid  bodies  must  be  broken  up  into  amino  acids  before  absorp- 
tion in  the  intestine  (p.  289).  If  this  be  true  then  ingestion  of 
the  cleavage  products  of  proteid  should  maintain  nitrogen 
equilibrium  in  the  same  way  as  the  ingestion  of  meat.  The 
first  experiments  in  this  direction  were  done  by  Loewi,"  who  gave 
a  dog  pancreas  which  had  been  self-digested  until  all  the  proteid 
had  been  converted  into  amino  acids,  as  was  indicated  by  the 
almost  complete  disappearance  of  the  biuret  reaction.  Fat  and 
carbohydrates  were  given  with  the  digest,  and  nitrogen  equilib- 
rium was  obtained  and  even  nitrogen  retention  accomplished. 
Thus,  in  one  experiment  covering  a  period  of  eleven  days,  pro- 
teolytic digestive  products  containing  an  average  of  6.08  grams 
of  nitrogen  were  given  daily,  of  which  only  5.19  grams  were 
eliminated  in  the  urine,  while  the  balance,  or  0.89  gram  of 
nitrogen,  was  retained  in  the  body  of  the  animal.  This 
amounted  to  9.79  grams  of  nitrogen  in  eleven  days.  Accom- 
panying this  nitrogen  retention  was  one  of  0.649  gram  of 
phosphoric  acid  (PjOj),  an  amount  larger  than  was  necessary 
for  the  upbuilding  of  new  tissue  from  the  nitrogen  compounds 
retained.  Loewi  concluded  that  he  had  demonstrated  the 
synthesis  of  new  proteid  within  the  organism. 

Lesser^  gave  a  pancreatic  digest  of  fibrin  to  a  dog  and  was 
unable  to  obtain  nitrogen  equilibrium. 

Henderson  and  Dean  ^  confirmed  Loewi  in  finding  that  they 
could  obtain  nitrogen  equilibrium  by  feeding  a  dog  with  the 


^  Kauffmann:  "Pfliiger's  Archiv,"  1905,  Bd.  cix,  p.  440. 
'  Loewi:  "Archiv  fiir  ex.  Path,  und  Pharm.,"  1902,  Bd.  xlviii,  p.  303. 
^  Lesser:  "Zeitschrift  fiir  Biologie,"  1904,  Bd.  xlv,  p.  506. 
^Henderson  and  Dean:  "American  Journal  of  Physiologic,"  1903,  vol.  i.x, 
386. 


104  SCIENCE   OF   NUTRITION. 

cleavage  products  of  meat  produced  by  treatment  with  sulphuric 
acid. 

Stiles  and  Lusk/  on  the  contrary,  gave  a  fasting  diabetic  dog 
a  pancreatic  digest  of  meat  which  had  undergone  fourteen 
months  of  proteolytic  cleavage,  and  observed  that  the  nitrogen 
of  it  was  completely  eliminated  in  the  urine  without  protecting 
the  body  from  loss  of  proteid,  w^hich  would  have  occurred  had 
meat  itself  been  administered. 

To  reconcile  these  differences  it  seemed  necessary  to  con- 
sider the  differences  in  methods  of  preparing  the  end  products 
of  the  proteid  to  be  ingested.  Indeed,  Abderhalden  and  Rona  ^ 
find  that  mice  live  on  casein  split  with  pancreatin  as  long  as  they 
do  on  casein  alone;  whereas  they  die  much  carHer  if  the  casein 
has  been  submitted  to  peptic  and  then  pancreatic  digestion,  or 
if  it  has  been  broken  up  by  acid  hydrolysis.  Henriques  and 
Hansen^  also  find  that  casein  broken,  up  by  acid  will  not  main- 
tain nitrogen  equilibrium  in  rats,  but  that  if  the  pancreas  of  the 
ox  and  a  small  piece  of  the  intestine  of  the  dog  (to  furnish  erepsin) 
be  digested  for  two  months  at  40°,  and  the  resulting  material  given 
to  rats,  nitrogen  equilibrium  will  be  maintained.  The  authors 
further  find  that  the  monoamino  acid  fraction  (the  filtrate  after 
precipitation  with  phospho  wolf  ramie  acid),  and  also  the  alco- 
holic extract  of  the  last-named  digest,  maintains  rats  in  nitrogen 
equilibrium.  The  residue  left  after  alcoholic  extraction  will 
not  do  so. 

Finally  Abderhalden  and  Rona  ^  have  accomplished  a  most 
interesting  experiment  upon  a  dog.  The  animal  was  given 
daily  a  constant  quantity  of  non-nitrogenous  foods  which  were : 
fat,  25  grams;  starch,  50  grams;  cane  sugar,  10  grams;  dex- 
trose, 5  grams.  The  dog  was  brought  into  nitrogen  equilibrium 
by  giving  meat  containing  2  grams  of  nitrogen.  Then  for  this 
were  substituted  the  amino  cleavage  products  of  casein,  pro- 

'  Stiles  and  Lusk:  "American  Journal  of  Physiology,"  1903,  vol.  ix,  p.  380. 
'Abderhalden  and  Rona:  "Zeitschrift  fiir  physiologische  Chemie,"   1904, 
Bd.  xlii,  p.  528. 

^  Henriques  and  Hansen:  Ibid.,  1905,  Bd.  .xliii,  p.  417. 
*  .Abderhalden  and  Rona:  Ibid.,  1905,  Bd.  xliv,  p.  198. 


THE    INFLUENCE    OF   PROTEID    FOOD.  I05 

duced  by  pancreatic  digestion  and  also  containing  2  grams  of 
nitrogen.  During  sixteen  days  on  this  diet  there  was  an  average 
daily  gain  of  0.12  grams  of  nitrogen  by  the  dog.  Then  casein 
hydrohzed  by  acid  and  containing  2  grams  of  nitrogen  was 
administered  for  ten  days,  during  which  time  the  dog  lost  0.48 
grams  of  nitrogen  daily.  Amino  products  prepared  after  this 
fashion  will  therefore  not  preserve  nitrogen  equiHbrium.  Lastly, 
the  diet  was  continued  without  any  nitrogenous  food.  The 
daily  waste  of  body  nitrogen  was  then  0.53  grams.  The  loss 
was  the  same  as  when  the  casein  hydrolized  by  acid  was  in- 
gested, indicating  that  this  particular  array  of  cleavage  prod- 
ucts had  no  protecting  power  over  the  body  proteid. 

The  absence  of  virtue  in  the  casein  hydrolized  by  acids  is 
attributed  by  Abderhalden  and  Rona  ^  to  the  complete  destruc- 
tion of  all  polypeptids  (p.  293)  which  are  probably  the  construc- 
tive nuclei  (Bausteine)  of  proteid.  When  the  latter  are  present 
a  partial  reconstruction  of  amino  acids  into  the  proteids  of 
blood  serum  is  possible. 

It  seems  therefore  proved  that  amino  bodies  resulting  from 
certain  proteolytic  cleavages  may  be  the  equivalent  in  metabo- 
lism of  ingested  proteid  itself. 

In  practical  dietetics  these  substances  can  have  no  value, 
as  they  tend  to  produce  diarrhea,  as  do  also  albumoses  and 
peptones  when  given  in  any  quantity.^  As  illustrating  this, 
Cohnheim^  finds  that  though  somatose  is  more  digestible  than 
meat,  still  over  30  grams  is  undesirable  in  the  daily  diet  of  a 
man. 

The  effect  of  copious  drinking  of  water  upon  proteid 
metabolism  has  been  made  the  subject  of  various  studies.  A 
small  increase  in  nitrogen  ehmination  has  usually  been  noted. 
This  was  first  estabhshed  by  Voit,  who  explained  it  as  due  to 
an  increased  circulation  which  influenced  the  flow  of  the  intra- 


'  Abderhalden   and  Rona:    "  Zeitschrift  fiir   physiol.    Chemie,"  1906,  Bd. 
xlvii,  p.  397. 

^  Voit:  "Miinchener  med.  Wochenschrift,"  1899,  Nos.  6  and  7. 
^  Cohnheim:  "Pfliiger's  Archiv,"  1904,  Bd.  cvi,  p.  17. 


Io6  SCIENCE   OF   NUTRITION. 

cellular  fluids.  Heilner^  has  recently  shown  that  giving  2000 
c.c.  of  water  to  a  fasting  dog  on  two  successive  days  raises  his 
urinary  nitrogen  from  3.15  grams  to  4.09  and  3.58  grams  on 
the  two  days  of  water  ingestion,  and  then  the  nitrogen  excretion 
falls  to  2.22  and  2.62  on  the  following  days.  In  this  experi- 
ment the  carbon  dioxid  excretion  was  Aery  slightly  increased 
and  the  temperature  of  the  dog  was  not  affected.  The  quantity 
of  urine  rose  from  90  c.c  to  2050  c.c. 

Straub^  found  that  an  extra  ingestion  of  2000  c.c.  of 
water  in  a  man  who  was  in  nitrogen  equilibrium  on  a 
diet  containing  20.56  grams  of  nitrogen  had  no  effect  on 
proteid  metabolism;  whereas  Hawk^  who  gave  less  proteid 
nitrogen  but  more  water,  found  that  the  ingestion  of  4500 
c.c.  of  water  caused  the  urinary  nitrogen  to  rise  from  11.03 
to  12.48  on  the  first  day,  and  11.82  on  the  second  day, 
with  a  fall  to  10.91  grams  on  the  succeeding  day  when  no  water 
was  given.  Hawk  interprets  the  action  of  copious  water  drink- 
ing as  twofold, — f^rst,  to  cause  a  removal  of  any  accumulation  of 
nitrogenous  decomposition  products  from  the  organism,  as  was 
indicated  by  the  greater  increase  of  12.8  per  cent,  in  the  nitrogen 
ehmination  of  the  first  day;  and,  second,  to  cause  a  true  in- 
crease in  proteid  metaboHsm  as  was  indicated  by  the  smaller 
increase  of  6.8  per  cent,  on  the  second  day  of  water  ingestion. 

One  of  the  striking  characteristics  of  starvation  metaboHsm 
was  shown  to  be  its  extreme  regularity  from  hour  to  hour  and 
from  day  to  day.  What,  then,  is  the  hour-to-hour  metaboHsm 
after  meat  ingestion? 

The  classical  experiments  of  Voit^  and  of  Feder^  have  been 
more  fully  worked  over  by  Gruber.  Gruber®  fed  a  dog  with 
500,  1000  and  1500  grams  of  meat  on  different  days.  He 
collected  the  urine  every  two  hours  after  the  meal  and  determined 

^  Heilner:  "Zeitschrift  fiir  Biologic,"  1906,  Bd.  xlvii,  p.  541. 

^  Straub:  Ibid.,  1899/ Bd.  xxxvii,  p.  527. 

^  Hawk:  "University  of  Pennsylvania  Medical  Bulletin,"  March,  1905. 

*  Voit:  "Physiologische  Untcrsuchungen,"  Augsburg,  1857,  p.  42. 

^  Feder:  "Zeitschrift  fiir  Biologie,"  1881,  Bd.  xvii,  p.  541. 

'  Gruber:  Ibid.,  1902,  Bd.  xlii,  p.  421. 


THE  INFLUENCE  OF  PROTEID  FOOD. 


107 


the  nitrogen  output.     The  curves  of  nitrogen  ehmination  under 
these  circumstances  are  as  follows: 

JV.in  s'''<^f^s  per  Zhrs. 


8 

1 

/ 

^\ 

\ 

£ 

^ 

/ 

\ 

\, 

/ 

\ 

< 

/ 

\ 

r 

~\ 

\ 

^1 

1 

/ 

V 

^. 

\ 

/ 

\ 

\ 

\ 

2 

Jl 

/^ 

■~^ 

\ 

\ 

K 

/ 

/ 

\ 

\ 

V 

£ 

2/ 

/ 

\ 

\ 

\ 

y 

\ 

N 

\ 

\ 

\ 

J 

\ 

\ 

N 

\ 

\ 

\^ 

■— 

— ' 

""^ 

( 

?  ^ 

y 

i 

5  i 

; 

c    1 

Z      1 

^  1 

6    / 

f     Z 

0    Z 

2  z^ 

Hoars 

Fig.  5. — I,  after  500  g.  meat  -^  50  g.  fat  +  350  c.c.  water;  2,  after  1000  g. 
meat  -i-  200  c.c.  water;  3,  after  1500  g.  meat  +  500  c.c.  water.  On  each  of  these 
days  the  animal  was  in  nitrogen  equilibrium. 

It  is  evident  that  there  is  an  early  elimination  of  proteid 
nitrogen  which  here  reaches  a  maximum  between  five  and  seven 
hours  after  feeding,  and  that  the  hour  of  the  maximum  excre- 
tion is  delayed  by  increasing  the  quantity  of  meat  ingested. 

It  is  apparent,  therefore,  that  the  proteid  metaboKsm  as  il- 
lustrated by  the  curve  of  nitrogen  elimination  is  quite  different 
from  the  even  metabolism  of  starvation. 

If  we  turn  from  the  nitrogen  ehmination  to  that  of  the  car- 
bon in  the  respiration,  it  will  be  found  that  here  the  elimina- 
tion is  comparatively  even.  Frank  and  Trommsdorf  ^  gave  a 
dog  1 191  grams  of  meat  which  had  been  freed  from  extractives 

^  Frank  and  Trommsdorf:  "Zeitschrift  fiir  Biologic,"  1902,  Bd.  xliii,  p.  266. 


io8 


SCIENCE   OF   NUTRITION. 


by  means  of  lukewarm  water.  The  nitrogen  and  carbon  of  the 
urine  and  feces,  and  the  carbon  of  the  respiration  were  deter- 
mined, and  from  these  data  the  proteid  and  fat  metaboHsm  were 
calculated  in  the  usual  manner.  From  this  the  heat  produced 
was  estimated.     The  essential  results  were  thus  tabulated : 

VARIATION  IN  METABOLISM  AFTER  MEAT  INGESTION. 


Period. 


Starvation 

Meat  Ingested; 

First  period  after  meat 
Second  "        "       " 
Third     "        "       " 
Fourth   "         "       " 


Per  Hour 


No.  OF  HonES. 


24 


4  h.  9  m. 
3  h.  14  m. 

5  h.  44  m- 
10  h.  53  m. 

(night) 


43-94 
41-53 
41.00 


It  is  evident  that  while  the  curve  of  the  nitrogen  elimination 
shows  a  ma.ximum  rise  to  nearly  eight  times  that  of  fasting  and 
varies  greatly,  the  carbon  curve  is  much  more  even  and  is  not 
much  above  that  found  in  starvation.  The  maximum  rise  in 
heat  production  occurs  in  the  first  four  hours  after  the  inges- 
tion of  meat  and  amounts  to  twenty  per  cent.  The  heat  pro- 
duction falls  during  the  night  hours. 

Rubner  ^  has  obtained  similar  results  after  giving  460  grams 
of  washed  meat  to  a  dog  weighing  24  kilograms.  His  calcula- 
tions show  the  following  metabolism  during  six-hour  periods: 

VARIATION  IN  METABOLISM  AFTER  MEAT  INGESTION. 


First  Day  of  Ingestion 

Time  of  Day. 

N  in  Urine. 

C=i'-  f^--^™  Pro-     Cal.  from  Fat. 

Calories  Total. 

Dav.     Q— 1 

5.06 
6.11 
4.64 
2.76 

18.6 

I35-I 

163.0 

123.8 

73-6 

495-5 

143-9 

85.2 

105.4 

169.5 

504.0 

279.0 

•3—0. 

248.2 

Night   9—^ 

229.2 

■t-r 

243-1 

Total 

999-5 

'  Rubner:  "Gesetze  des  Energieverbrauchs,"  1902,  p.  365. 


THE    INFLUENCE   OF   PROTEID    FOOD.  1 09 

VARIATION  IN  METABOLISM  AFTER  MEAT  INGESTION 
{Cotrtinned). 


Third  Day  of  Ingestion. 


Time  of  Day. 

N.  in  Urine. 

Cal.  from   Pro- 
teid. 

Cal.  from  Fat. 

Calories  Total. 

Day,     Q— ■? 

5-57 
8-94 
5-32 
2.66 

22-5 

148.7 

238.7 

142.0 

71.0 

600.4 

130.4 
33-4 
76.3 

162.4 

402.5 

279.1 
272.1 
218.3 
233-4 

1002.9 

3-9 

Night,  9-3 

3^ 

_  Total 

The  nitrogen  curve  varies.  The  total  heat  production  is 
greatest  during  the  hours  immediately  following  the  ingestion 
of  proteid,  but  is  otherwise  comparatively  even. 

If  we  pass  from  the  consideration  of  proteid  metabohsm,  as 
indicated  by  the  nitrogen  curve,  to  the  consideration  of  the 
intermediary  metabolism  of  proteid  we  can  see  more  clearly  that 
the  curve  of  proteid  nitrogen  excretion  is  not  a  true  index  to 
the  sum  of  the  activities  contributed  to  the  cells  by  proteid 
metabolism. 

Voit^  believed  that  there  was  an  early  cleavage  of  the  pro- 
teid molecule  into  a  nitrogenous  portion  and  a  non-nitrogenous 
portion,  a  cleavage  involving  the  liberation  of  only  a  small 
amount  of  energy;  that  there  was  a  rapid  combustion  of 
the  nitrogenous  radicle,  as  shown  by  the  elimination  of  the 
nitrogenous  end-products  in  the  urine;  and  that  the  non- 
nitrogenous  radicle  which  contained  the  major  part  of  the 
potential  energy  of  the  proteid  molecule  might  in  part  be  tem- 
porarily stored  either  as  glycogen  or  fat  and  be  gradually  doled 
out  to  the  tissues  as  the  need  required. 

Claude  Bernard  believed  that  glycogen  could  arise  from 
proteid.  Wolffberg  ^  let  fowls  fast  two  days  to  remove  the  gly- 
cogen and  then  for  two  days  gave  meat  powder  which  was 

^  Voit:  "Zeitschrift  fiir  Biologie,"  1891,  Bd.  xxviii,  p.  291. 
''Wolffberg:  Ibid.,  1876,  Bd.  xii,  p.  27S. 


no  SCIENCE   OF  NUTRITION. 

free  from  carbohydrate.  Two  fowls,  killed  during  the  inter- 
val of  proteid  digestion,  showed  considerable  glycogen  in 
their  livers  (1.56  and  1.45  per  cent.)  and  muscles  (0.251 
and  0.454  per  cent.),  much  more  than  would  have  been 
present  in  starvation.  Two  similar  fowls,  killed  seventeen  and 
twenty-four  hours  after  the  last  proteid  ingestion,  contained 
much  less  glycogen  in  their  Hvers  (0.145  ^^^  0.22  per  cent.)  and 
muscles  (0.211  and  0.162  per  cent.).  This  origin  of  glycogen 
from  proteid  was  fully  confirmed  by  Kiilz^  in  a  very  extended 
series  of  experiments  in  which  chopped  meat,  fully  extracted 
with  warm  water,  was  made  the  basis  of  the  ingesta.  It  be- 
came evident  from  these  experiments  that  if  sufficient  proteid 
were  given  to  an  animal,  part  of  the  proteid  carbon  could  be 
retained  as  glycogen. 

It  has  long  been  believed  that  sugar  arises  from  proteid  in 
diabetes.  Kossel'  first  suggested  that  hexone  bases,  leucin,  and 
other  proteid  end-products,  contained  six  atoms  of  carbon  as 
did  also  the  ordinary  hexose  sugars,  such  as  dextrose,  levulose 
and  galactose.  The  theory  of  the  origin  of  sugar  in  diabetes 
from  these  amino  products  was  strongly  advocated  by  Friedrich 
Miiller.^  The  definite  proof  of  this  was  afforded  by  Stiles  and 
Lusk*  who  gave  a  mixture  of  amino  bodies  prepared  by  the  pan- 
creatic proteolysis  of  meat  to  a  dog  rendered  diabetic  with 
phlorhizin.  The  mixture  was  free  from  proteid.  The  nitrogen 
ingested  was  entirely  eliminated  in  the  urine,  and  for  each 
gram  of  such  nitrogen  2.4  grams  of  extra  sugar  appeared  in  the 
urine. 

A  little  farther  on  it  will  be  shown  how  such  a  body  as  leucin 
of  the  general  formula  CgNHj  may  be  denitrogenized  ^  and  in 
part  converted  into  dextrose  (p.  232).     Knopf^  has  sho^\^l  that 

'  Kiilz:  "Ludwig's  Festschrift,"  1890,  p.  83. 

^Kossel:  "Deutsche  medizinische  Wochenschrift,"  1898,  p.  58. 

^  Miiller  and  Seeman:  Ibid.,  1899,  p.  209. 

*  Stiles  and  Lusk:  "American  Journal  of  Physiolog}',"  1903,  vol.  9,  p.  380. 

'  Halsey:  "American  Journal  of  Physiology,"  1904,  vol.  x,  p.  229. 

'  Knopf:  "Archiv  fiir  ex.  Path,  und  Pharm.,"  1903,  Bd.  xlix,  p.  123. 


THE    INFLUENCE    OF   PROTEID    FOOD.  Ill 

other  amino  bodies,  like  asparagin,  which  do  not  contain  six 
atoms  of  carbon  are  likewise  convertible  into  dextrose  in  the 
body.  (See  chapter  on  Diabetes.)  Considerable  sugar  may 
therefore  originate  from  proteid  in  the  course  of  its  ordinary 
metabolism.  The  question  arises  at  what  time  during  the 
metabolism  does  this  sugar  become  available  for  combustion  in 
the  organism  ?  This  question  was  answered  by  an  experi- 
ment of  Reilly,  Nolan,  and  Lusk.^  These  authors  gave  a 
fasting  phlorhizinized  dog  500  grams  of  meat  and  collected  the 
urine  in  two  3-  and  one  6-hour  periods.  The  results  were  as 
follows : 

EXCRETION    OF    DEXTROSE    AND    NITROGEN    BEFORE    AND 
AFTER  INGESTING  500  GRAMS  OF  MEAT  IN  DIABETES. 

Dextrose.        Nitrogen.  D:N. 

Preceding  3  hours 5.96  1.75  3.41 

First      3  hours  after  feeding 12.43  2.52  4.92 

Second  3     "         "           "      i4-7o  3.76  3.91 

Third   3     "         "          "       11.23  3-85  2.92 

Fourth  3     "         "           "       11-23  3.85  2.92 

Following  3  hours 6.34  1.78  3.56 

The  normal  fasting  relation  between  dextrose  and  nitrogen 
changed  immediately  upon  the  ingestion  of  meat.  During  the 
first  hours  more*  dextrose  was  eliminated  than  corresponded 
to  the  nitrogen  in  the  urine.  During  the  later  hours  this  pro- 
portion was  reversed.  The  sugar  elimination  therefore  took 
place  decidedly  before  that  of  the  nitrogen.  This  is  shown  in 
the  following  calculation  of  the  percentage  elimination  of 
nitrogen  and  dextrose  in  3-hour  periods  following  the  ingestion 
of  500  grams  of  meat  in  the  above  experiment: 


Dextrose.  Nitrogen. 

During  first        3  hours 26.06  18.02 

"        second  3        "     29.64  26.90 

"        third      3        "     22.65  27.54 

fourth    3       "    22.65  27.54 

100.00  100.00 

^  Reilly,  Nolan,  and  Lusk:  "American  Journal  of  Physiology,"  1898,  vol.  i, 
P-  395- 


112  SCIENXE    OF    NUTRITION. 

The  relations  arc  represented  in  the  following  curve: 


4 


grants  D.  for  Shrs 


Ndrqsert. 

Dextrose. 

Fig,    6. — Curve   showing   the   elimination   of   dextrose   before    nitrogen    after 
meat  ingestion  (500  grams)  in  diabetes. 

That  the  dextrose  production  from  the  meat  ingested  was 
proportional  to  the  proteid  destroyed  is  evident  from  the  follow- 
ing comparison,  in  which  the  sum  of  the  dextrose  and  nitrogen 
eliminated  in  the  twelve  hours  is  considered.  Nitrogen  and 
dextrose  double  in  quantity  after  the  ingestion  of  meat,  but 
their  relative  amount  remains  the  same  as  in  starvation. 


Fasting  1 2  hours 

After  500  g.  meat,  12  hours. 
Subsequent  1 2  hours 


Dextrose. 
■    23.87 
49-50 
25-36 


Nitrogen. 

7.00 

14.00 


I):X. 

3-41 
3-54 
3-56 


The  curve  shows  that  there  is  an  early  production  of  sugar 
from  proteid  which  may  be  liberated  in  metabolism  before  the 
nitrogen  belonging  to  the  proteid  is  eliminated  in  the  urine.  A 
similar  early  production  of  sugar  from  proteid  has  also  been  ob- 
served after  feeding  dogs  with  meat  in  pancreas  diabetes.^ 

Since  one  gram  of  nitrogen  in  the  urine  represents  a  destruc- 
tion of  6.25  grams  of  meat  proteid,  and  since  there  is  simultane- 

1  Berger:  Inaugural  Dissertation,  Halle  (Nebelthau),  1901;  cited  from  Maly's 
"  J ahresbcricht  iiber  Thierchemie,"  Bd.  xxxi,  p.  848. 


THE  INFLUENCE  OF  PROTEID  FOOD.  II3 

ously  an  average  elimination  of  3.65  grams  of  dextrose  in  phlor- 
hizin  diabetes,  it  may  be  calculated  that  the  sugar  production 
from  meat  amounts  to  58  per  cent,  by  weight  of  the  meat  pro- 
teid  metaboHzed  and  may  contain  52.5  per  cent,  of  its  total 
available  energy  (p.  64). 

After  the  ingestion  of  proteid  in  the  normal  organism  this 
sugar  early  becomes  available  and  may  be  burned  before  the 
nitrogen  belonging  to  it  is  eliminated,  or  if  the  sugar  be  formed 
in  excess,  it  may  be  stored  as  glycogen  in  the  liver  and  muscles 
of  the  body  for  subsequent  use.  In  this  way  it  is  obvious  that 
at  least  half  the  energy  in  proteid  may  be  independent  of  the 
curve  of  nitrogen  elimination,  but  may  rather  act  as  though  it 
had  been  ingested  in  the  form  of  carbohydrate.  Carbohydrates 
when  ingested  do  not  cause  a  rise  in  the  production  of  heat, 
but  may  simply  burn  as  needed  by  the  cells.  This  will  be 
explained  in  the  next  chapter.  It  is  therefore  evident  that 
this  carbohydrate,  which  is  early  supplied  in  the  breaking 
down  of  proteid,  may  distribute  its  energy  according  to  the  re- 
quirement of  the  cells  as  long  as  it  lasts.  This  is  apparently 
the  principal  cause  of  the  evenness  of  the  carbon  dioxid  excre- 
tion as  contrasted  with  the  great  irregularity  of  the  nitrogen 
elimination  after  proteid  ingestion. 

It  has  been  noted  that  Frank  and  Trommsdorf,  and  Rubner 
also,  in  experiments  previously  mentioned,  calculated  the  heat 
production  during  the  first  few  hours  after  feeding  with  meat  ac- 
cording to  the  usual  method  from  the  data  furnished  by  the 
nitrogen  and  carbon  ehmination.  This,  however,  will  not  tell 
the  exact  truth  regarding  the  fat  and  proteid  metabolism  during 
a  short  period,  for  dextrose  from  proteid  may  be  burning, 
which  is  not  indicated  by  the  nitrogen  excretion  of  the  time. 
The  error  here  introduced  would  not  be  large,  but  a  correction 
would  tend  to  reduce  somewhat  the  calculated  heat  production 
during  the  period  immediately  following  the  ingestion  of  meat. 
This  experiment  should  be  controlled  by  simultaneous  measure- 
ments with  an  animal  calorimeter.  It  is  obvious  that  respira- 
tion experiments  extending  over  a  few  hours  cannot  so  accurately 


114 


SCIENCE   OF   NUTRITION. 


present  the  picture  of  the  metabohsm  after  feeding  with  meat  as 
they  do  in  the  case  of  starvation,  where  the  intermediary  metabo- 
hsm is  a  constant  and  even  factor. 

Concerning  the  intermediate  metabohsm  of  proteid,  it  is  fur- 
ther shown  from  the  work  of  Parker  and  Lusk'  that  the  inges- 
tion of  casein  by  rabbits  maintained  under  the  influence  of  ben- 
zoic acid  results  in  an  ehmination  of  hippuric  acid  which  is 
proportional  to  the  proteid  metabohsm.  This  is  illustrated  in 
the  following  table: 


CONSTANT   RELATION    BETWEEN   GLYCOCOLL   PRODL'CTION 
AND  N  ELIMINATION  AFTER  INGESTING  PROTEID. 


Day. 

Casein  In- 
gested    IN 
Grams. 

Benzoic 
Acid  given 
IN    Grams. 

Grams     Hip- 
puric Acid  Ex- 
creted. 

Total  N 
Excreted 
in   Grams. 

Hippuric  Acid 
N:  Total  N. 

First  

Second  

Third 

4 

5 

lO 

I 
I 
1-5 

.7230 

•7575 
1.0302 

1.469 
1.456 
1.929 

1:25.9 
1:24.6 
1:23.9 

Total  nitrogen  and  hippuric  acid  output  maintain  the  same 
ratio  throughout  the  above  experiment. 

It  may  be  estimated  that  casein  yields  3.45  per  cent,  of  gly- 
cocoll  in  metabolism  as  compared  with  3.98  per  cent,  obtained 
when  body  proteid  metabolizes  in  starvation  (p.  64).  This 
experiment  seems  remarkable  because  the  chemist  has  not  been 
able  to  obtain  glycocoll  from  casein. 

Magnus-Levy,^  apparently  using  the  same  method,  finds 
that  25  to  27  per  cent,  of  the  total  urinary  nitrogen  of  rabbits 
fed  with  cream  and  of  a  goat  fed  with  hay  is  excreted  in  the 
form  of  hippuric  acid.  He  calculated  that  only  4  per  cent,  of 
this  could  have  been  derived  from  glycocoll  preformed  in  the  pro- 
teid metabolized,  but  that  20  per  cent,  could  have  originated 
from  leucin  in  passing  through  a  glycocoll  stage.  Why  Parker 
and  Lusk  obtained  the  4  per  cent,  elimination  and  Magnus- 
Levy  secured  one  of  25  per  cent,  is  not  at  present  clear. 

'  Parker  and  Lusk:  "American  Journal  of  Physiology,"  1900,  vol.  iii,  p.  472. 
^  Magnus-Levy:  "Miinchener  med.  Wochenschrift,"  1905,  Bd.  Hi,  p.  2168. 


THE  INFLUENCE  OF  PROTEID  FOOD.  II5 

The  writer  has  unsuccessfully  endeavored  to  bring  about 
an  ehmination  of  cystein,  the  sulphur-containing  compound 
in  the  proteid  complex,  by  constant  treatment  of  a  dog  with 
benzol  chlorid.  It  is  possible  that  the  bromid  or  iodid  might 
be  successfully  used. 

Since  the  last  sentence  was  written  the  work  of  Wolf  ^  has 
been  published,  which  shows  that  after  frequent  administration 
of  benzol  bromid  to  a  dog,  an  artificial  cystinuria  is  brought 
about.  The  benzol  bromid  unites  with  the  cystein  liberated  in 
proteid  metabolism  and  the  compound,  a  mercapturic  acid,  is 
ehminated  in  the  urine.  In  this  way  Wolf  increased  fourfold  the 
unoxidized  sulphur  (cystein-S)  in  the  urine,  and  nearly  removed 
all  the  inorganic  sulphate  from  the  urine,  although  curiously 
enough  there  was  a  shght  increase  in  the  quantity  of  ethereal 
sulphates  present.  Folin  and  Alsberg^  investigated  a  case  of 
cystinuria  and  found  similar  relations.  The  increase  in  neutral 
sulphur  was  at  the  expense  of  alkaline  sulphate  in  the  urine.  The 
cystein  elimination  was  increased  by  increasing  the  proteid  in 
the  food. 

Friedmann  ^  shows  that  the  cystein  of  mercapturic  acid  is  the 
same  cystein  as  may  be  obtained  on  the  cleavage  of  proteid  in  the 
laboratory. 

If  cystein  be  administered  to  a  normal  person  it  is  burned  and 
does  not  alter  the  normal  relation  between  oxidized  and  unox- 
idized sulphur  in  the  urine. ^ 

That  cystein  is  the  mother  substance  of  the  taurin  of  the  bile 
Friedmann^  illustrates  in  accordance  with  the  following  formulae: 

c  H2  SH  c  H2  SO3  H  CH3SO3H 

CHNH2+3O  =  CHN  H2  —  CO2  =   C  H,  N  H2 

C  OOH  COOH 

Cystein.  Cysteinic  acid.  Taurin. 

^  Mariott  and  Wolf:  "American  Medicine,"  1905,  vol.  ix,  p.  1026. 

^  Folin  and  Alsberg:  "American  Journal  of  Physiology,"  1905,  vol.  xiv,  p.  54. 

^Friedmann:  "Hofmeister's  Beitrage,"  1904,  Bd.  iv,  p.  486. 

^Blum:  Ibid.,  1904,  Bd.  v,  p.  i. 

^  Friedmann:  Ibid.,  1902,  Bd.  iii,  p.  i. 


ii6 


SCIENCE    OF   NUTRITION. 


The  indications  are  that  cystcin  is  a  normal  product  of  pro- 
teid  metabolism  which  a  patient  suffering  from  cystinuria  is 
unable  to  burn. 

In  a  phenomenon  called  alcaptonuria  tyrosin  and  phenyla- 
lanin  are  oxidized  only  as  far  as  the  alcaptonic  acids,  which  are 
uroleucinic  and  homogentisic  acids,  and  in  this  form  they  appear 
in  the  urine.  Their  production  from  phenylalanin  according 
to  Falta  *  is  as  follows : 


Hor 


OH 


Hor 


JOH 


CH, 

CH, 

CH, 

CH2 

CHNHj 

CHOH 

CHOH 

1 

COOH 

COOH 

COOH 

COOH 

Phenylalanin.         Phenyl-a-lactic  acid.       Uroleucinic  acid.       Homogentisic  acid. 

He  finds  that  if  phenylalanin  or  tyrosin  are  administered  in 
alcaptonuria,  they  are  completely  converted  into  the  alcaptonic 
acids  and  so  eliminated.  In  alcaptonuria  the  ratio  between 
homogentisic  acid  and  nitrogen  elimination  in  the  urine  is 
constant,  being  45:100^  while  the  distribution  of  the  various 
other  nitrogenous  compounds  in  the  urine  remains  normal. 
Garrod  and  Hale^  find  the  same  ratio  as  above  and  believe  with 
Falta  that  where  this  error  in  normal  metaboHsm  occurs  it  is 
complete  in  the  sense  that  the  homogentisic  acid  excreted  repre- 
sents the  whole  of  the  tyrosin  and  phenylalanin  of  the  proteids 
broken  down. 

Neubauer  and  Falta*  have  recently  emphasized  the  idea  that 
the  alcaptonic  acids  are  always  formed  in  normal  metabolism, 
but  in  this  rare  disease  cannot  be  further  oxidized. 


'  Falta:  "Biochemisches  Centralblatt,"  1904,  Bd.  iii,  p.  175. 

^  Langstein  and  Meyer:  "Deutsches  Archivfijr  klin.  Med.,"  1903,  Bd.  l.x.xviii; 
Schumm:  "Miinchener  med.  Wochenschrift,"  1904,  Bd.  xxxvi,  p.  1599. 

^  Garrod  and  Hale:  "Journal  of  Physiology,"  1905,  vol.  xxxiii,  p.  205. 

*  Neubauer  and  Falta:  "Zeitschrift  fiir  physiologische  Chemie,"  1904, 
Bd.  xlii,  p.  81. 


THE   INFLUENCE    OF   PROTEID    FOOD.  II7 

Sugar,  glycocoll,  cystein,  and  the  alcaptonic  acids  are  there- 
fore products  of  proteid  metabohsm  whose  excretion  may  be 
brought  about  by  special  means  or  by  certain  pathological  con- 
ditions. 

Kynurenic  acid,  which  is  frequently  found  in  dogs'  urine, 
has  acquired  new  interest  since  Ellinger's  ^  discovery  that  if  a 
dog  be  given  tryptophan — a  product  of  proteolysis — the  kynu- 
renic acid  is  greatly  increased  in  the  urine.  Mendel  and  Jackson- 
found  that  the  kynurenic  acid  elimination  in  dogs  varied  directly 
with  the  proteid  metabolism  but  was  not  derived  from  gelatin 
metabolism.  Ellinger^  has  fed  a  rabbit,  whose  urine  normally 
contains  no  kynurenic  acid,  with  tryptophan,  and  found  kynu- 
renic acid  in  the  urine.  Rabbits,  however,  normally  burn 
kynurenic  acid  when  ingested  in  small  amounts.  He  reaches  the 
conclusion  that  animals  in  general  may  produce  kynurenic  acid 
from  tryptophan  in  proteid  metabohsm,  and  that  this  is 
usually  readily  oxidized,  except  in  the  organism  of  the  dog, 
w^here  it  is  only  partly  destroyed  and  therefore  appears  in  the 
urine. 

There  is  a  nitrogenous  end-product  normally  present  in  the 
urine  the  origin  of  which  is  obscure,  and  this  is  creatinin. 

Voit^  found  that  while  muscle  contained  creatin,  the  urine 
if  it  were  acid  contained  creatinin;  otherwise  creatin  appeared. 
Urinary  acid  phosphate  causes  the  dehydration  of  creatin  into 
creatinin  in  the  kidney.  Voit  showed  that  ingested  creatin  was 
completely  eliminated  in  the  urine,  and  that  the  amount  in  the 
urine  after  meat  ingestion  was  the  quantity  contained  in  the 
meat  metabolized. 

Following  this  line  of  research,  Gruber^  gave  a  dog  1500 
grams  of  meat  daily  and  noticed  the  constancy  of  the  relation  be- 
tween the  total  nitrogen  and  creatinin  in  the  urine.  There  was 
no  relatively  increased  creatinin  elimination  during  starvation 

*  Ellinger:  "Zeitschrift  fiir  physiologische  Chemie,  "1904,  Bd.  xliii,  p.  325. 
'  Mendel  and  Jackson:  "American  Journal  of  Physiology,"  1898,  vol.  ii,  p.  i. 
^  Ellinger:  Loc.  cit. 

*  Voit:  "Zeitschrift  fiir  Biologie,"  1868,  Bd.  iv,  p.  77. 

*  Gruber:  Voit's  Festschrift,  "Zeitschrift  fiir  Biologie,"  1901,  Bd.  xlii,  p.  416. 


ii8 


SCIENCE  OF  NUTRITION. 


following  on  a  period  of   excessive  ingestion  of  meat  which 
showed  that  creatin  had  not  been  stored  up  in  the  body. 
The  results  of  these  experiments  are  as  follows: 

CREATININ  ELIMINATION  AFTER  MEAT  INGESTION. 


Day. 

Food. 

N  IN  Urine. 

Creatinin  in 
Urine. 

Creatinin  :  N. 

First  

Second  

Third 

Fourth 

Fifth 

Sixth 

1500  g.  meat, 
starvation. 

41.20 
47.60 
4567 
"■35 
6.97 

5-98 

3.916 
4.I19 

4-054 
0.478 
0.469 
0.569 

I  :  10.52 

I  :  "-55 
I  :  11.26 
I  :  23.74 
I  :  14.85 
I  :  10.53 

The  complete  elimination  of  ingested  creatin  observed  by 
Voit  has  been  fully  confirmed  by  Mallet.* 

Creatin,  therefore,  is  not  a  precursor  of  urea,  since  it  passes 
through  the  organism  unchanged.  Nor  does  the  amount  of  urea 
produced  influence  the  elimination  of  creatinin.  Fohn^  has 
recently  shown  that  on  a  creatin-free  diet  (such  as  milk  and 
cream)  the  amount  of  creatinin-nitrogen  in  the  urine  is  0.6 
gram,  whether  the  total  nitrogen  in  the  urine  be  16.8  or  3.6 
grams.  Folin  regards  this  small  quantity  of  creatin  as  a  con- 
stant product  of  the  essential  breakdown  of  living  cell  proteid 

(P-  293)- 

Ph.  Munk^  says  that  in  convalescence  the  required  amount 

of  creatin  is  retained  for  the  upbuilding  of  new  tissue.  Crea- 
tinin is  absent  in  the  urine  of  milk-fed  children/  presumably 
for  the  same  reason.  It  would  be  interesting  in  the  light  of 
Folin's  work  to  see  whether  on  a  milk  diet  in  convalescence 
creatinin  would  disappear  from  the  urine.  Its  absence  would 
confirm  Munk's  theory.  Cellular  metabolism  may  perhaps 
prepare  for  new  muscle  protoplasm  a  constituent  not  imme- 
diately derivable  from  the  milk  casein. 

*  Mallet:  U.  S.  Dept.  of  Agriculture,  1899,  Bulletin  66. 

^  Folin:  "American  Journal  of  Physiology,"  1905,  vol.  xiii,  p.  117. 
'  Munk:  "Deutsche  Klinik,"  1862,  p.  300. 

*  Rietschel:  "  Jahrbuch  fiir  Kinderheilkunde,"  1905,  Bd.  xli,  p.  4. 


THE    INFLUENCE    OF   PROTEID    FOOD'.  II9 

Creatin  is  the  extractive  existing  in  larger  quantity  than  any 
other  in  muscle.  It  is  one  of  the  principal  constituents  of 
Liebig's  extract  of  beef.  Such  an  extract,  which  contains  also 
xanthin,  is  not  strictly  a  food,  since  its  constituents  are  largely 
ready  for  ehmination  in  the  urine. ^  Biirgi'  shows  that  if 
meat  extract  be  administered  it  is  excreted  in  the  urine  ex- 
cepting 4.57  per  cent,  of  its  nitrogen,  14.85  per  cent,  of  its  car- 
bon, and  17.55  P^r  cent,  of  its  energy  content. 

Its  value  lies  in  its  f-uvor,  which  promotes  the  proper  flow 
of  the  digestive  juices.^ 

It  may  be  incidentally  remarked  that  the  principal  value  of 
"patent"  foods  hes  in  their  flavor.  If  agreeable  to  the  taste 
of  the  individual  they  usually  afford  a  harmless  indulgence. 
That  beef,  milk,  cream,  butter,  and  rice  are  equally  suitable 
for  all  the  purposes  of  proper  hving  is  a  fact  not  sufficiently  ad- 
vertised. The  old-time  fraud  of  "patent"  foods  being  "brain 
restorers"  is  as  foohsh  a  lie  as  can  be  \\Titten. 

Rubner*  says  that  the  rise  of  the  curve  of  sulphur  elimination 
precedes  that  of  nitrogen,  while  that  of  the  phosphate  elimina- 
tion follows  it.  The  experiment  is  on  the  dog  already  described 
(page  109)  during  the  6-hour  periods  following  an  ingestion  of 
460  grams  of  washed  meat.  The  following  represents  the  per- 
centage ehmination  of  nitrogen,  sulphur  and  phosphorus  during 
6-hour  interv^als  on  the  third  feeding  day.  Of  100  per  cent, 
there  were  excreted: 

N. 

During  the  first        6  hours 24.8 

"      second  6      "      39-8 

"       third     6      "      23.6 

"       fourth   6      "      1 1.8 

Sherman  and  Hawk,^  however,  give  curves  showing  beauti- 

'  Rubner:  "Zeitschrift  fiir  Biologie,"  1883,  Bd.  xix,  p.  343. 

^  Burgi:  "Archiv  fur  Hygiene,"  1904,  Bd.  li,  p.  i. 

^Voit:  "Stoffwechsel,"  1882,  p.  449. 

*  Rubner:  "Energiegesetze,"  1902,  p.  368. 

^  Sherman  and  Hawk:  "Am.  Jour,  of  Physiology,"  1900,  vol.  iv,  p.  43. 


s. 

36.7 

P2O5. 
16.0 

31-7 

32.1 

21. 1 

33-4 

IO-5 

18.5 

I20 


SCIENCE   OF   NUTRITION. 


fully  an  almost  parallel  elimination  of  sulphur  and  nitrogen  in 
man  on  a  mixed  diet.     A  curve  showing  this  is  here  presented: 


8     DAY 


2-^0 


2ca 


Fig.  7. — The  curves  here  shown  represent  the  relative  fluctuations  in  the 
average  rates  of  excretion  of  nitrogen  and  SO3.  The  values  on  the  left  represent 
percentages  of  an  assumed  standard  rate  of  excretion  for  each  of  these  constitu- 
ents. It  will  be  seen  that  in  general  the  excretion  of  sulphates  ran  quite  closely 
parallel  to  that  of  nitrogen. 


This  discussion  of  the  ehmination  of  various  intermediary 
products  of  proteid  metabolism  Ufts  the  veil  from  hidden 
factors  sufficiently  to  give  a  ghmpse  into  a  field  of  increasingly 
fruitful  investigation. 

A  question  which  has  aroused  great  interest  has  been  that 
concerning  the  production  of  fat  from  proteid.  Pettenkofer 
and  Voit  ^  found  that  after  ingesting  considerable  quantities  of 
proteid,  although  the  nitrogen  of  the  proteid  was  eliminated  in 
the  urine,  a  part  of  the  carbon  was  retained  in  the  body  and 
not  excreted  by  the  usual  channels.  They  estimated  that  meat 
proteid  contained  3.68  grams  of  carbon  to  each  gram  of  nitrogen. 
If  less  than  3.68  grams  of  carbon  appeared  in  the  total  excreta 
when  one  gram  of  nitrogen  was  eliminated,  then  some  pro- 
teid carbon  must  have  been  stored  in  the  body.  This  carbon 
might  have  been  retained  in  two  forms — as  glycogen  or  as  fat. 
Claude  Bernard  had  showTi  that  glycogen  increases  in  the  liver 
after  the  ingestion  of  proteid.     The  retained  carbon  as  ob- 


*  Pettenkofer   and   Voit: 
Supplement,  pp.  52  and  361. 


Annalen  der  Chemie    und    Pharm.,"    1S62,    IJ 


THE   INFLUENCE    OF   PROTEID    FOOD.  121 

served  by  Pettenkofer  and  Voit  was  in  such  large  quantity  as  to 
preclude  the  possibihty  of  its  retention  entirely  as  glycogen,  and 
therefore  they  concluded  that  fat  must  have  been  prepared  from 
proteid  and  stored  up  in  the  body.  This  afforded  an  experi- 
mental basis  for  the  theory  of  a  production  of  fat  from  proteid 
in  fatty  degeneration. 

Later  Rubner/  in  Voit's  laboratory,  showed  that  the  re- 
lation 3.68  C:  I  N  in  proteid,  as  used  by  Pettenkofer  and  Voit, 
was  erroneous,  and  that  meat  fully  extracted  with  ether  contains 
only  3.28  of  carbon  to  one  of  nitrogen.  The  polemical  arraign- 
ment by  Pfliiger"  of  Voit's  older  work  was  based  upon  these 
results  of  Rubner.  Instead  of  there  being  a  great  retention  of 
proteid  carbon,  there  was  none  in  some  experiments  and  very 
little  in  others.  The  formation  of  fat  from  proteid  was  evidently 
less  easy  of  demonstration  than  it  had  seemed. 

The  subject  was  investigated  anew  by  Cremer,^  who  starved 
a  cat  for  many  days,  and  then  gave  the  animal  all  the  lean  meat 
it  would  eat,  or  about  450  grams  a  day.  The  cat  was  kept 
in  a  respiration  apparatus  and  the  total  excreta  were  collected. 
The  carbon  belonging  to  the  meat  ingested  was  calculated  at  the 
low  ratio  of  3.18  to  i  of  nitrogen.  The  average  daily  metabolism 
during  the  eight  days  of  meat  ingestion  is  indicated  in  the  follow- 
ing table: 

Weights  in  Grams. 

Meat  C  calcu-  C    from    meat 

N   in  urine                           C  in                                lated      from  added  to  the 

and  feces,     Urine,     Feces,    Respiration,         N  excreted,  the  body, 

13.0               7.5          1.4               25.4                       41-6  7.3  ' 

34-3 

There  was  a  daily  excretion  of  13  grams  of  nitrogen  corre- 
sponding to  the  liberation  of  41.6  grams  (13X3. 18)  of  proteid 
carbon.  But  only  34.3  grams  of  carbon  were  actually  elimi- 
nated from  the  body,  and  a  difference  of  7.3  grams  was  re- 

'  Rubner:  "Zeitschrift  fur  Biologie,"  1885,  Bd.  xxi,  p.  324. 

^Pfliiger:  "Pfhiger's  Archiv,"  1892,  Bd.  lii,  p.  239. 

^  Cremer:  "Zeitschrift  fiir  Biologie,"  1899,  Bd.  xxxviii,  p.  309. 


122 


SCIENCE   OF   NUTRITION. 


taincd  in  the  body;  17.5  per  cent,  of  the  proteid  carbon  there- 
fore was  not  ehminated.  For  eight  days  the  whole  carbon 
retention  was  58  grams,  which  corresponds  to  a  glycogen  produc- 
tion of  130  grams.  The  cat,  however,  contained  only  35  grams 
of  glycogen,  determined  after  kiUing  it  at  the  end  of  the  experi- 
ment. The  balance  of  the  carbon  must  have  been  stored  as 
fat. 

Cremer'  notes  that  a  cat  fed  as  above  contains  1.47  per  cent, 
of  muscle  glycogen,  which  is  as  much  as  the  maximum  (1.37 
per  cent.)  found  by  E.  Voit  in  geese  after  the  ingestion  of  starch. 

Since  it  is  known  that  sugar  in  excess  may  be  converted  into 
body  fat  and  that  meat  may  yield  58  per  cent,  of  sugar  in  metab- 
olism, there  is  every  reason  to  believe  that  if  proteid  be  ingested 
in  excess  this  sugar  may  be  converted  into  glycogen  and  then,  if 
the  quantity  be  sufficient,  into  fat. 

It  is  quite  possible  that  the  origin  of  fat  from  proteid  is  in 
its  nature  the  same  as  the  origin  of  fat  from  carbohydrates. 

Rubner^  has  noted  a  similar  carbon  retention  after  the  inges- 
tion of  proteid  in  excess.     Two  examples  of  this  may  be  cited.^ 

The  first  experiment  was  upon  a  dog  which  had  been  reduced 
by  starvation  from  a  weight  of  11  to  6  kilograms.  He  was  then 
given  500  grams  of  meat  a  day. 

CARBON  RETENTION  AFTER  PROTEID  INGESTION. 


Day. 


Food. 


First Starvation. 

Second Starvation. 

Third 500  g.  meat. 

Fourth 500  g.  meat. 


N    IN 

Ex- 
creta. 

C     FROM 

Fat  Meta- 
bolism. 

I-3I 

1-52 

13-05 
14.20 

22.46 

19.77 

(-^.87) 

(-2.41) 

Calor- 
ies 

FROM 

Pro- 
teid. 


Calories 
from 
Fat. 


32.7s  275.2 

38.00,  243-2 

339-3  I  —8.9 

355.0  I  —24.9 


Total 
^^^-       Body 

/Sl^VEIOHT 

bolism. 


308.0  I  5.94 

281.2  5.82 

330.4  5.86 

330.1  !  6.00 


This  experiment  shows  that  on  the  first  day  of  meat  ingestion 
0.87  gram  of  carbon  from  proteid  was  retained  in  the  dog  and  on 

'Cramer:  "Zeitschrift  fur  Biologic,"  1899,  Bd.  xxxviii,  p.  313. 
^  Rubner:  "Gesetze  des  Energieverbrauchs,"  1902,  pp.  57,  84. 
'  For  a  third  example  see  this  book,  table  on  p.  128. 


THE    INFLUENCE    OF   PROTEID    FOOD. 


12- 


the  second  day  2.41  grams  were  so  retained.  Rubner^  has 
calculated  that  the  carbon  in  the  respiration  derived  from  pro- 
teid  has  a  calorific  value  of  10.2  calories  per  gram.  When  pro- 
teid  carbon  is  retained  in  the  body,  its  heat  equivalent  must  be 
deducted  from  the  heat  value  of  the  proteid  metabolism  as  com- 
puted from  the  nitrogen  in  the  excreta,  in  order  to  obtain  the 
true  total  of  heat  liberated.  This  heat  value  of  retained  carbon 
is  a  little  above  the  calorific  value  of  carbon  in  dextrose,  which 
is  9.4  calories  per  gram. 

The  second  experiment  which  may  be  cited  was  done  by 
Rubner  upon  a  large  dog  which  was  given  2000  grams  of  meat 
at  a  time.     The  results  were  as  follows : 

CARBON  RETENTION  AFTER  PROTEID  INGESTION. 


Food. 

Excreta. 

Calories. 

Day. 

Kind. 

N. 

Cal. 

N. 

Fate. 

Proteid. 

Fat. 

Total. 

First 

Starv. 

Starv. 
2000  g. 

meat. 

Starv. 
2000   g. 

meat. 

Starv. 

68 
68 

1926 
1926 

5.01 

5. 10 

51.60 

12.39 
52.68 

12.18 

48.19 

49.90 

(-29-58) 

37-19 
(-26.58) 

36.82 

125.75 
128.00 
1351-9 

325-62 
1380.22 

319-12 

592.72 

613-77 

— 305.66 

420.54 
—274-57 

452.89 

718.49 
741-77 
1046.34 

746-16 
1105.65 

772.01 

Second 

Third 

Fourth 

Fifth 

Sixth 

On  both  days  when  2000  grams  of  meat  were  ingested,  carbon 
was  retained  in  the  organism  either  as  glycogen  or  fat.  On  the 
first  of  these  days  17.7  per  cent,  of  the  total  proteid  carbon  was 
retained,  which  corresponds  to  17.5  per  cent,  found  by  Cremer 
in  the  cat  during  a  prolonged  period  of  proteid  diet.  The 
writer,  on  the  basis  of  his  work  on  diabetes,  computes  that  44 
per  cent,  of  the  total  carbon  in  meat  proteid  may  be  converted 
into  dextrose  (p.  112).  It  is  known  that  sugar  is  convertible 
into  fat  (p.  150).  If  44  per  cent,  of  proteid  carbon  may  be 
converted  into  dextrose  and  under  other  conditions  17.5  per 
cent,  may  be  converted  into  fat,  it  is  evident  that  of  the  total 
dextrose-carbon  which  may  be  produced  in  proteid  metabolism, 

'  Rubner:  "Zeitschrift  ftir  Biologic,"  1885,  Bd.  xxi,  p.  363. 


124  SCIENCE   OF   NUTRITION. 

40  per  cent,  can  be  converted  into  fat-carbon  (p.  151).  There 
seems  to  be  no  doubt  that  protcid  may  in  part  be  converted 
first  into  glycogen  and  then  into  fat  after  excessive  proteid 
ingestion.  The  question  of  a  "fatty  degeneration"  of  proteid 
under  pathological  conditions  is  another  matter  and  will  be  con- 
sidered at  another  time.     (See  Chapter  XII.) 

These  last  two  experiments  of  Rubner's  bring  to  light  a  very 
striking  change  in  the  metabolism  after  the  ingestion  of  proteid 
in  excess.  The  total  heat  production  is  markedly  increased. 
To  what  may  this  be  due  ? 

Mering  and  Zuntz  ^  beheved  that  such  increased  metabolism 
was  due  to  the  activity  of  the  intestinal  tract  after  the  ingestion 
of  food. 

Voit^  criticised  this  view  and  said  that  a  rise  in  the  carbon 
dioxid  excretion,  from  366  grams  in  starvation  to  783  grams 
after  ingestion  of  meat  in  excess,  was  too  great  to  be  due  to 
intestinal  activity,  and,  indeed,  corresponded  to  the  rise  noted 
only  after  the  hardest  exercise.  Furthermore,  Voit  had 
shown  that  after  giving  a  medium  quantity  of  fat,  the  carbon 
dioxid  excretion  and  oxygen  absorption  were  almost  the  same  as 
in  hunger,  notwithstanding  the  activity  of  the  filled  intestine. 

This  question  has  received  very  painstaking  and  elaborate 
investigation  at  the  hands  of  Rubner,  who  has  pubHshed  his 
results  in  a  book  entitled  "Die  Gesetze  des  Energieverbrauchs 
bei  der  Emahrung."  This  volume  is  an  extension  of  a  work  of 
which  a  preliminary  communication  was  published  by  Rubner' 
from  Voit's  Munich  laboratory  in  1885.  During  subsequent 
years  of  continued  activity  the  doctrines  were  more  and  more 
firmly  established. 

Rubner  shows  that  bones  given  to  a  dog  will  not  increase  his 
metabolism,  in  spite  of  the  intestinal  irritation,  so  the  increase 
after  meat  ingestion  is  not  due  to  a  nerve  retiex  of  mechanical 


'  Mering  and  Zuntz:  "  Pfliiger's  Archiv,"  1877,  Bd.  xv,  p.  634. 
^  Voit:  "Physiologic  des  allegemeinenen  Stoffwechsel,"  1881,  p.  209. 
^Rubner:    " Sitzungsberichte  d.  kgl.  bayr.  Acad.  d.  Wissenschaft,"  li. 
Heft  4. 


THE    INFLUENCE    OF   PROTEID    FOOD.  1 25 

nature.  Further,  the  metabohsm  is  not  raised  after  the  ingestion 
of  meat  extract,  so  the  chemical  stimulus  of  flavors  which  start 
activity  in  the  glands  does  not  affect  total  metabolism.  Again, 
the  ingestion  of  water  in  the  quantity  contained  in  meat,  while  it 
may  cause  a  rise  in  nitrogen  in  the  urine  followed  by  a  fall — the 
rise  being  due  to  a  rapid  washing  out  of  nitrogenous  decomposi- 
tion products — does  not  alter  the  total  metabolism  in  any  way. 

Rubner  determined  the  starvation  metabolism  and  used 
this  as  a  unit  for  the  measurement  of  the  absolute  "require- 
ment" of  the  organism.  This  "requirement"  of  energy  may 
be  met  by  the  ingestion  of  an  equivalent  "maintenance  diet" 
which  covers  the  requirement.  An  "abundant  diet"  contains 
a  larger  amount  of  potential  energy  than  the  organism  requires. 

Rubner  at  first  found  that  if  the  food  ingested  had  a  lower 
calorific  value  than  the  body's  requirement,  then  the  metabohsm 
was  not  usually  increased  after  the  ingestion.  This  is  illus- 
trated in  one  of  his  earher  experiments  ^  summarized  below. 

Food.  Metabolism  in  Calories. 

Starvation 867 

Bones,  40  grams 812 

Meat,  720  grams 836 

Meat,  760  grams 875 

So  if  the  food  contains  less  than  the  energy  requirement,  the 
metabohsm  may  not  be  increased  in  spite  of  activity  of  the  glands 
and  muscles  of  the  intestinal  tract. 

To  explain  this  Rubner  -  introduced  his  compensation  theory. 
This  assumed  a  certain  reciprocity  between  the  muscles  and 
the  glands.  During  starvation  and  medium  temperature,  a  great 
part  of  the  body's  heat  is  produced  in  the  muscles,  and  those 
cells  ordinarily  concerned  in  taking  up  food  are  quiet  and  pro- 
duce little  heat.  On  warming  the  outside  air  the  amount  of 
metabolism  in  the  muscles  decreases.  The  same  thing  may  take 
place  when  gland  cells  and  intestinal  musculature  are  thrown 
into  activity,  the  voluntary  muscles  are  proportionally  relieved. 

^  Rubner:  "  Zeitschrift  fiir  Biologic,"  1883,  Bd.  xix,  p.  349. 
^  Rubner:  "Die  Gesetze  des  Energieverbrauchs,"  1902,  p.  8. 


126  SCIENCE    OF    NUTRITION. 

Quite  a  different  picture  is  presented  when  an  abundant 
diet  is  supplied  to  the  dog.  If  proteid  above  the  calorific  re- 
quirement be  ingested  there  is  a  very  considerable  rise  in  the 
heat  production.  This  increase  is  greater  in  the  case  of  proteid 
than  with  any  other  foodstuff.  Rubner  calls  this  action  of 
abundant  proteid  food  in  raising  the  metabolism  the  specific 
dynamic  action  of  proteid.  This  action  is  shown  in  the  two 
experiments  of  Rubner  cited  on  pages  122,  123.  In  the  second 
experiment,  the  total  metabohsm  during  the  starvation  days  is 
as  follows: 

First  day 718.5  calories. 

Second  dav 741-8 

Third  day'. 7462 

Fourth  day 772.0 

Rubner  took  the  average  of  the  last  two  days  as  representing 
the  requirement  in  starvation,  or  759.1  calories.  After  admin- 
istering 2000  grams  of  meat  containing  1962  calories,  or  the  full 
starvation  requirement  and  153.7  per  cent,  besides,  the  heat 
production  rose  from  759.1  calories  to  1046.34  and  1105.65 
calories, — that  is,  it  increased  42.2  and  45.6  per  cent.  Rubner 
recalculated  the  calories  produced  by  the  metabolism  during 
the  experiment  on  the  assumption  that  the  carbon  from  pro- 
teid was  retained  as  glycogen  and  not  as  fat,  and  in  this  way 
estimated  the  increased  metabolism  after  this  ingestion  of  meat 
at  45.5  and  48.7  per  cent,  above  the  starvation  minimum. 

Combining  the  results  of  such  experiments,  Rubner^  finds 
the  following  increasing  specific  dynamic  effect  of  proteid  as 
the  quantity  above  the  requirement  becomes  larger. 

Excess  above  Increase  in  Heat 

Requirement.  Production. 

56  per  cent ig  per  cent. 

90        "       35 

105        "       44 

153        "       49 

Here  were  increases  in  total  metabolism  comparable  to  those 
induced  by  considerable  mechanical  work.     The  body  metabo- 

'  "Rubner:  "Gesetze  des  Energieverbrauchs,"  p.  90. 


THE  INFLUENCE  OF  PROTEID  FOOD.  1 27 

lized  in  largely  increased  measure  without  doing  any  external 
work. 

A  more  rapid  respiration  alone  betokened  the  increased 
oxidation  and  the  effort  of  the  body  to  rid  itself  of  excess  of  heat 
through  physical  regulation.  The  temperature  of  the  dogs 
scarcely  changed,  so  perfect  is  the  regulatory  mechanism  for 
the  discharge  of  heat.  Thus  in  one  dog  the  temperature  was 
38.16°  before  the  meal,  38.74°  during  the  digestion,  and  38.17° 
at  the  end  of  digestion. 

Rubner  differentiated  between  three  stages  of  proteid  metab- 
olism. First,  in  the  cases  of  undernutrition  and  of  mainte- 
nance diet  in  which  proteid  enters  into  the  circulation  and  spares 
an  isodynamic  quantity  of  the  body  substances;  second,  the  state 
of  abundant  nutrition  where  the  proteid  raises  the  metaboHsm 
through  its  specific  dynamic  power;  third,  an  intermediary  stage 
where  proteid  may  be  added  as  tissue  to  the  body  without  in- 
creasing the  metabohsm.  This  period  of  "pure  deposit"  of  tis- 
sue may  rapidly  pass  into  the  stage  of  deposit  united  with  specific 
action  causing  increase  in  combustion.  It  will  be  apparent 
later  that  the  first  and  third  states  of  proteid  nutrition  can  be 
achieved  only  at  low  or  medium  temperatures  of  environment. 

An  example  of  the  stage  of  the  deposit  of  proteid  tissue 
without  a  rise  in  metabolism  is  given  by  Rubner^  as  follows: 

N  TO  Body.  Calories  per  Kg. 

Starvation 45.61 

Starvation 43.26 

Meat +8.7  44.48 

Meat +4.7  46.16 

This  kind  of  growth  of  tissue  without  a  corresponding  rise 
in  metaboHsm  takes  place  in  the  normal  adult  only  when  the 
proteid  ingested  is  below  the  heat  value  of  the  fasting  metabo- 
lism. If,  however,  a  larger  quantity  of  proteid  be  ingested  than 
the  heat  requirement  of  the  body  calls  for,  then  the  usual 
specific  dynamic  action  occurs  and  also  a  continued  "  secondary" 
rise  in  total  day-to-day  metabolism,  which  increases  as  long  as 

^  Rubner:  "Gesetze  des  Energieverbrauchs,"  p.  256. 


128  SCIENCE   OF   NUTRITION. 

proteid  is  deposited.     When  nitrogen  equilibrium  is  established 
the  heat  production  remains  constant  at  a  higher  level. 

Rubner^  illustrates  this  important  fact  in  the  following  ex- 
periment on  a  dog: 


M^I^^O.  NTOBOOV.      CARBOXTOBODV.      '''^'^^l^!^  '^ 


o    — I-3I  ■  ■-  310.61 

o    — 1.52  .  ..  278.00 

481.5 3-95  2.97  3"-43 

481.5 2.80  3.70  2:^^.82 

481.5 2.30  i.6r  368.41 

481.5 2.20  2.53  361.70 

481.5 0.92  4.45  375-47 

481.5 0.20  4.31  395-77 

o    —3-70  •  ■■  357-20 

o    — 2.64  .  ..  310.29 

The  constant  deposit  of  proteid  therefore  continually  raises 
the  heat  production  in  the  organism  until  a  point  is  reached 
when  no  more  proteid  is  added  to  the  body.  This  is  the  point 
of  nitrogenous  equilibrium,  and  is  very  quickly  attained.  It 
is  evident  that  on  a  purely  proteid  diet  no  great  addition  of 
proteid  tissue  can  ever  take  place  in  the  adult  on  account  of  this 
secondary  dynamic  action,  which  causes  a  constantly  increasing 
combustion,  thereby  bringing  about  nitrogenous  equihbrium. 

Rubner  shows  that  the  retention  of  fat  from  proteid  in  the 
body  has  nothing  to  do  with  this  action.  Proteid  retention  is 
much  more  readily  brought  about  on  a  mixed  diet  containing 
large  quantities  of  carbohydrates,  as  will  be  seen  in  a  subsequent 
chapter. 

Up  to  the  present  writing  the  influence  of  external  tem- 
perature upon  the  course  of  proteid  metaboHsm  has  not  been 
discussed.  Rubner  has  shown  that  this  is  a  factor  of  profound 
significance.  It  has  already  been  demonstrated  how,  through 
chemical  regulation,  the  basal  requirement  of  the  body  is  reflexly 
increased  by  increasing  cold  in  the  environment.  Rubner' 
compared  the  starving  metaboHsm  of  a  dog  at  different  tem- 
peratures with  that  of  the  same  dog  when  100,  200,  and  320 
grams  of  meat  were  ingested.     The  results  are  presented  as 

'  Rubner:  "Die  Qesetze  des  Energieverbrauchs,"  1902,  p.  246. 
^  Rubner:  Ibid.,  p.  109. 


THE   INFLUENCE    OF   PROTEID    FOOD. 


129 


follows  in  terms  of  calories  produced  per  kilogram  of  body- 
weight  : 

INFLUENCE   OF  EXTERNAL  TEAIPERATURE   ON  METABOLISM 
AFTER  PROTEID  INGESTION. 


Temperature. 

Starv.\tion. 

100  Gm.  Meat  or 
24  Cal.  per  Kg. 

200  Gm.  Meat  or  ;  320  Gm.  Meat  or 
48  Cal.  per  Kg.  |  Si  Cal.  per  Kg. 

7° 

i;^ 

86.4 
63.0 

55-9 
54-2 
56.2 

55-9 
55-5 
55-6 

77-7 

57-9 
64.9 

63-4 

87.9 
86.6 

20° 

76-3 
83.0' 

25" 

30° 

One  hundred  grams  of  meat  did  not  change  the  metabolism 
at  20°,  25°,  or  30°;  200  grams  of  meat  had  no  effect  at  20°  or  at 
7°,  but  at  25°  and  at  30°  there  was  an  increase  although  the  food 
contained  fewer  calories  than  the  requirement.  With  320 
grams  of  meat  there  was  a  great  increase  above  the  starvation 
requirement,  except  at  7°,  where  it  is  a  maintenance  diet  and  the 
metaboKsm  remains  unchanged.  In  other  words  at  a  tem- 
perature of  30°  the  specific  dynamic  action  of  this  amount  of 
proteid  is  capable  of  increasing  the  heat  production  above  that 
of  starvation  by  about  53  per  cent.,  while  at  7°  there  is  no 
change  whatever.  It  is  also  evident  that  at  a  high  temperature 
even  a  small  quantity  of  proteid  such  as  200  grams  meat  causes 
a  considerable  rise  of  metabolism. 

Rubner  gives  the  metabolism  in  terms  of  calories  per  kilo- 
gram after  the  ingestion'  of  550  grams  of  meat  or  173.8  calories 
per  kilogram  of  body  weight  in  a  dog,  as  follows : 


Tempera- 
ture. 

Starva- 
tion. 

4.2°.. 

.128.1 

14-5°-- 
22.1°.. 
30.7°.. 

.  .100.9 
..   70.7 
..   62.0 

550  Grams 

Me 

4T. 

Increase. 

133-5 

4.2  per  cent 

1 10.9 

9.9      " 

lOI.O 

42.9      " 

117. 2 

89.0      " 

These  experiments  make  evident  the  extraordinary  influence 
of  variations  in  the  surrounding  temperature  on  the  metaboUsm 
when  the  same  quantity  of  meat  is  fed.     The  influence  of  tem- 
perature must  therefore  be  continually  kept  in  mind  as  a  most 
9 


130  SCIENCE   OF   NUTRITION. 

important  factor  of  the  amount  of  the  metabolism.  jSIany  ex- 
periments reported  as  having  been  done  at  the  "room  tempera- 
ture" have  an  indefinite  value. 

An  additional  point  of  interest  is  that  in  certain  cases  the 
number  of  calories  remains  constant  throughout  the  experiment, 
notwithstanding  a  variation  in  the  temperature.  This  is  show^n 
on  ]).  129,  where  the  dog  was  given  320  grams  of  meat.  The 
amount  of  the  metabolism  scarcely  varied  with  the  temperature. 
The  chemical  regulation,  or  the  increased  heat  production 
brought  about  by  a  reduction  of  the  surrounding  temperature,  is 
not  evident  in  this  case.  Here  the  fuel  value  of  the  food  was  equal 
to  the  requirement  of  the  body  even  at  a  temperature  of  7°. 

From  the  general  results  of  these  experiments  Rubner^ 
deduces  two  important  laws  w'hich  govern  metabolism  as  in- 
fluenced by  temperature.  Their  significance  will  be  better  ap- 
preciated in  the  analysis  of  the  subject  in  the  following  chapter. 

"  The  first  laic  is  that  within  limits  normally  compatible  with 
life,  warm-blooded  animals  are  capable  0}  adapting  themselves  to 
change  in  external  temperature  through  a  reflex  increase  or  de- 
crease oj  the  activity  of  their  heat- producing  apparatus.  For 
every  state  of  body  substance  and  for  every  temperature  of  the 
environment  there  is  a  definite  amount  of  heat  loss  to  which  the 
organism — with  the  aid  of  its  heat-regulating  apparatus — tends 
to  approach.  This  may  be  called  the  minimal  heat  requirement. 
There  is  no  law  enforced  with  greater  severity  or  fatality.  The 
starving  man  who  lives  on  his  own  substance  cannot  remove 
himself  from  its  influence.     Inexorable  until  the  last  hour  of  Hfe 

it  demands  fulfilment It  kills  the  starving  child  in 

days,  while  it  allows  the  starving  adult  weeks." 

"The  second  law  concerning  the  relation  of  external  tem- 
perature to  the  organism  is:  The  physical  regulation  can  never 
enter  as  a  factor  unless  the  conditions  of  the  first  law  are  fully 
satisfied,  i.  e.,  until  the  heat  production  equals  the  requirement 
of  the  organism.  If,  however,  the  heat  production  be  greater  than 
corresponds  to  the  minimal  requirement  for  that  temperature,  then 

'  Rubner:  "Die  Gesetze  des  Energieverbrauchs,"  1902,  p.  160. 


THE    INFLUENCE    OF    PROTEID    FOOD. 


131 


the  heat  production  within  certain  limits  remains  independent  0}  the 
temperature.  Under  these  circumstances  the  heat  production  does 
not  decrease  on  raising  the  external  temperature,  and  only  increases 
when  through  increasing  cold  the  former  heat  production  no  longer 
covers  the  minimal  requirement  of  the  organism  for  heat." 

This  second  law  explains  why  in  certain  cases  after  food 
ingestion  the  carbon  dioxid  excretion  may  remain  constant 
with  changing  temperatures.  Its  action  is  seen  in  the  dog 
mentioned  on  page  129,  after  he  had  eaten  320  grams  of  meat  at 
various  temperatures.  The  increase  in  body  metabolism  due 
to  the  stimulus  of  cold  (chemical  regulation)  is  not  necessary, 
since  heat  in  excess  of  the  requirement  is  already  available,  x^ll 
that  is  needed  is  the  arrangement  of  avenues  of  escape  for  the 
excess  of  heat  produced  from  the  food  ingested  (physical  regula- 
tion). This  physical  regidation  is  brought  about  by  the  evapora- 
tion of  water  and  by  the  distribution  of  the  blood. 

How  the  increased  evaporation  of  water  enters  as  a  refrigerat- 
ing factor  is  beautifully  shown  in  the  experiment  on  the  dog 
(p.  129)  which  fasted  and  then  received  100,  200,  and  320 
grams  of  meat  at  various  temperatures.  The  distribution  of 
the  loss  of  heat  by  radiation  and  conduction  and  by  the  evapora- 
tion of  water  was  as  follows: 

DISTRIBUTION    OF   HEAT   LOSS     FROM   A   DOG   AFTER   MEAT 

INGESTION. 


Hun 

100  Grams 

200  Grams 

320  Grams 

Meat. 

Meat. 

Meat. 

■s  c 

0    . 

c 
0   . 

■3  c 

§   . 

•3  a 

2 

a 

0   . 
■3  c 

a.  >-. 

c3  0 

aC 

Temperature. 

-Si 

^ 

5| 

II 

a  0 

11 

^  c 

13 

n 

11 

.•^ 

.  c 

.  C 

.  c 

tS   ■' 

rf 

a 

u 

U 

u 

u 

u 

u 

0        1    U 

I 

7° 

78.5 

7-9 

67.1 

10.6 

78-5         9-4 

11:° 

55-3 

7-7 

. .  . 

a6    7               T  T     ^ 

76.2 

10.4 

20"= 

45-3 

10.6 

46.7 

9.2 

49-5 

15-4 

.  -  . 

21;'= 

41.0 
33-2 

13.2 
23.0 

50^ 

34-1 

21.5 

27.8 

35-6 

34-5 

48.S 

132  .  SCIENCE   OF   NUTRITION. 

It  is  evident  from  the  above  that  the  greater  part  of  the  loss 
of  heat  at  a  low  temperature  was  by  radiation  and  conduction, 
but  at  a  high  temperature  (30°)  the  loss  by  the  evaporation  of 
water  was  largely  increased.  The  increased  heat  production, 
on  account  of  the  specific  dynamic  action  of  the  proteid,  was 
lost  through  the  increased  evaporation  of  water. 

Much  meat  on  a  hot  day  would  therefore  seem  contraindi- 
cated. 

While  the  chemical  regulation  protects  the  body  from  an 
abnormal  fall  in  temperature,  the  physical  regulation  prevents  an 
abnormal  rise  in  temperature.  The  organism  may  be  at  times 
under  the  influence  of  one  means  of  regulation,  at  times  of  the 
other,  and  without  being  conscious  of  any  difference. 

Cold-blooded  animals  have  no  chemical  regulation,  and 
their  temperature  falls  with  that  of  their  surroundings. 

The  following  chapter  will  more  fully  discuss  the  cause  of 
the  specific  dynamic  action  of  the  foodstuffs. 


CHAPTER  VI. 

THE  SPECIFIC  DYNAMIC  ACTION  OF  THE  FOOD- 
STUFFS. 

A  study  of  the  specific  dynamic  action  of  proteid  in  its  re- 
lation to  temperature  changes  gave  Rubner  ^  new  points  of  view. 
He  saw  (experiment  on  p.  129)  that  by  chemical  regulation  the 
metabolism  in  a  fasting  dog  was  increased  from  54  to  86  calories 
per  kilogram,  an  increment  of  32.  And  he  likewise  observed 
after  the  ingestion  of  320  grams  of  meat  that  the  heat  produced 
at  a  room  temperature  of  30°  rose  from  56  in  starvation  to  83,  a 
difference  of  27  calories.  The  source  of  the  increase  through 
chemical  regulation  is  known  to  be  chiefly  in  the  muscles.  The 
increase  brought  about  by  proteid  ingestion  had  been  shown  by 
Rubner  to  be  due  not  to  any  such  thing  as  intestinal  activity 
(Darmarbeit)  but  rather  to  some  specific  heat-raising  effect  of 
proteid  metabohsm  itself.  It  was  apparent  that  these  two 
sources  of  increased  heat  might  enter  into  a  reciprocal  arrange- 
ment because  on  coohng  the  atmosphere  in  which  the  dog  hved 
to  7°  C,  the  metabohsm,  after  the  ingestion  of  320  grams  of  meat, 
remained  at  87.9  calories  in  contrast  with  83.0  on  feeding  at 
30°.  Here  the  calories  of  the  specific  d}Tiamic  action  were  used 
in  replacement  of  the  calories  through  the  chemical  regula- 
tion. This  illustrates  Rubner's  modified  idea  of  his  compen- 
sation theory,  or  a  reciprocity  between  heat  produced  in  the 
muscles  by  chemical  regulation  and  the  extra  heat  production 
brought  about  through  the  ingestion  of  food. 

Since  the  extra  heat  production  after  food  ingestion  could 
be  utihzed  instead  of  heat  from  chemical  regulation,  Rubner 
perceived  that  the  true  increase  through  specific  d}Tiamic  action 
could  be  measured  only  at  the  temperature  of  33°,  where  there 
was  no  reflex  increase  in  metabolism  through  chemical  regulation. 

^  Rubner:  "Energiegesetze,"  p.  145. 
133 


134 


SCIENCE    OF    NUTRITION. 


It  was  especially  important  to  make  experiments  regarding 
the  action  of  foodstuffs  at  a  temperature  of  t,t^°,  for  that  is  the 
temperature  with  which  man  surrounds  his  skin.  By  means 
of  clothes  and  artificial  heating  man  constantly  tries  to  re- 
move himself  from  the  influence  of  chemical  regulation.  His 
daily  Hfe  is  practically  under  the  influence  of  a  tropical  cHmate. 
His  metabolism  is  unchanged  from  the  normal  when  he  is  im- 
mersed in  a  bath  at  ^2i°-^ 

Rubner  therefore  planned  an  experiment  in  which  a  dog  was 
kept  at  a  temperature  of  t,^°.  At  times  the  animal  fasted  in  order 
that  the  basal  requirement  could  be  determined,  and  during 
other  definite  periods,  meat,  fat,  and  carbohydrates,  either 
alone  or  combined,  were  ingested,  and  the  increased  metabo- 
lism due  to  the  varying  dietaries  was  noticed.  The  experiment 
extended  over  a  period  of  forty-six  days. 

A  summary  of  the  results  obtained  is  shown  in  the  following 
table  and  is  graphically  illustrated  by  the  accompanying  figure 
8,  which  has  been  taken  from  Rubner.' 


TABLE  INDICATING  THE  SPECIFIC  DYNAMIC  ACTION  OF  DIF- 
FERENT  FOODSTUFFS    AT   33°. 

Values  in  Calories  per  Kilogram  Body  Weight. 


Diet* 

Hunger 
Require- 
ment. 

Food  In- 
gested. 

Proteid 
Ingested. 

Metab- 
olism. 

Increase  ABOVE 

Hunger  in  per 

cent. 

100  per  cent,  fat 

54-0 

53-4 

60.9 

12.7 

66  per  cent,  meat  . . 

53-5 

37-7 

3^-3 

62.1 

16.0 

10  per  cent,  meat  ^, 
90  per  cent.  fat..   / 

53-4 

55-5 

5-1 

60.6 

13-4 

20  per  cent,  meat    ; 
80  per  cent.  fat. .   / 

52-5 

59-3 

10.5 

63.6 

2r.5 

100  per  cent,  meat  .. 

52.0 

63.0 

57-1 

73-8 

41.C) 

Aleat,  fat,  sugar 

51.0 

59-8 

8.8 

55-6 

9.0 

100  per  cent,  meat  .. 

51.0 

60.3 

56.3 

67.3 

31.0 

Meat,  fat,  starch 

50.0 

48.0 

8.1 

53-0 

4.0 

87  per  cent,  sugar.. 

50.0 

43-6 

52.5 

5-0 

66  per  cent,  meat  .. 

50.0 

34-5 

31-6 

60.4 

20.8 

*  Percentages  are  in  terras  of  the  starvation  requirement  and  are  approrimate  only. 


■  Rubner:  "  Archiv  fiir  Hygiene,"  1903,  Bd.  xlvi,  p.  390. 
:  "Energiegesetze,"  p.  324. 


'  Rubner:  "Archiv  fiir  Hygl 
'Rubner:  "Energiegesetze," 


SPECIFIC    DYNAMIC    ACTION    OF    FOODSTUFFS. 


135 


It  is  clearly  evident  that  meat  ingestion  raises  the  metabo- 
lism most,  fat  next,  and  sugar  least  of  all  the  foodstuffs.  The 
ingestion  of  the  starvation  requirement  for  energy  in  the  form 
of  fat  raises  the  metabohsm  12.7  per  cent.  During  the  two 
periods  when  approximately  100  per  cent,  of  the  basal  require- 
ment was  ingested  as  meat  there  was  an  average  increase  in 
the  metabolism  of  36.7  per  cent. 


Msa 

t 

r^ 

10 

% 

u 

r-Fat 

M 

at 

it 

U 

Tl 

>© 

/ 

Fa!t 

dot'} 

n 

Ml 

at 

Hurii 

er 





Hun 

^er 

-  — 

— 

—  _ 



— 

H 

tnge 

■ 



._ 



1 

P 

zy^. 

- 

"^ 

•lur 

,ir 

U^ 

■*:S 

"  ^ 

•. 

0       "s 

V 

0 

^ 

9         t 

' 

' 

'       ' 

/ 

"  Dei. 

/s 

^ 

M 

xjser 

in 

■te 

nt.'' 

t 

* 

Fig.  8. — Rubner's  chart  indicating  the  specific  dynamic  action  of  different 
foodstuffs  ingested  at  a  room  temperature  of  33°.  The  dotted  line  indicates 
the  height  of  the  fasting  metabohsm.  ^ 


More  detailed  examination,  however,  reveals  the  fact  that 
the  exact  quantity  of  meat  ingested  contained  119. 6  per  cent, 
of  the  basal  requirement  of  calories,  of  which  iio.i  were  con- 
tained in  meat  proteid  and  the  balance  in  fat  present  in  the  meat. 
If  under  the  influence  of  the  ingestion  of  11 9.6  per  cent,  of  the 
basal  requirement  the  metabohsm  rose  36.7  per  cent.,  then  the 
increase  due  to  the  ingestion  of  100  per  cent,  would  have  been 
30.74  per  cent.     But  this  meat  containing  100  per  cent  of  the 


136  SCIENCE   OF   NUTRITION. 

basal  requirement  in  reality  consisted  of  meat  proteid  contain- 
ing 92.06  per  cent,  of  the  energy  and  of  fat  containing  the  re- 
maining 7.94  per  cent.  Since  the  ingestion  of  fat  sufficient  to 
provide  100  per  cent,  of  the  basal  requirement  for  energy  raises 
metabolism  12.7  per  cent.,  then  fat  sufficient  to  provide  7.94 
per  cent,  of  the  basal  requirement  must  increase  metaboUsm 
7.94  X  0.127  or  i.oi  per  cent. 

Deducting  this  i.oi  per  cent,  which  is  due  to  the  specific 
dynamic  action  of  the  fat  ingestion  from  the  total  increase  of 
30.74  per  cent,  it  is  found  that  29.73  per  cent,  increase  is  due  to 
the  92.06  per  cent,  of  pure  meat  proteid  ingested. 

If  92.06  per  cent,  of  meat  proteid  raises  the  metabohsm 
29.73  per  cent,  then  100  per  cent,  of  such  proteid  will  increase 
it  by  32.28  per  cent.  Using  the  same  procedure  in  computing 
the  heat-raising  power  of  two-thirds  the  basal  requirement  of 
energy  for  the  dog,  ingested  in  the  form  of  meat,  it  was  calcu- 
lated that  if  100  per  cent,  of  the  requirement  had  been  the 
quantity  supphed  the  increase  in  the  metabolism  would  have 
been  29.60  per  cent.     Rubner  therefore  found  that — 

I.  After  ingesting  meat  in  excess  of  the  starvation  metabo- 
lism, the  specific  dynamic  action  caused  a  heat  increase  of  32.28 
per  cent. 

II.  After  ingestion  of  a  smaller  quantity  the  specific  dynamic 
action  similarly  measured  was  29.60  per  cent. 

The  average  of  these,  or  30.94  per  cent.,  represents  the 
specific  dynamic  action  of  proteid  or  the  increased  heat  pro- 
duction after  the  ingestion  of  meat  containing  100  per  cent,  of 
the  energy  requirement,  when  the  animal  is  outside  of  the 
influence  of  the  chemical  regulation. 

In  another  case,  after  the  ingestion  of  meat  in  large  excess, 
Rubner  finds  the  increase  due  to  the  specific  dynamic  action  to 
be  32.2  per  cent.  The  action  of  gelatin  is  similar,  the  increase 
in  metabolism  being  28.0  per  cent,  for  every  100  calories  in 
the  gelatin  ingested. 

Again  Rubner^  has  determined  the  amount  of  the  metabol- 

'  Rubner:  "Energiegesetze,"  p.  370. 


SPECIFIC   DYNAMIC   ACTION   OF   FOODSTUFFS.  137 

ism  of  a  fasting  dog  and  that  of  the  same  dog  made  diabetic 
with  phlorhizin  (see  p.  237).  Under  the  latter  circumstances 
the  proteid  metabohsm  is  greatly  increased.  He  found  that  for 
every  100  calories  increase  in  body  proteid  broken  down  there 
was  an  increased  heat  production  of  31.9  calories.  Here  was  a 
rise  in  heat  production  not  due  to  proteid  ingestion  and  there- 
fore not  due  to  intestinal  work,  but  due  to  the  mere  fact  of 
increased  proteid  metabohsm  in  starvation.  The  specific 
dynamic  action  of  proteid  then  may  thus  be  tabulated: 

Inxreased  Heat  Production  for  every  100  Calories 
Ingested  or  Metabolized. 

Meat  proteid 30.9 

Gelatin 28. o 

Body  proteid  (phlorhizin  diabetes) 31.9 

Considering  the  conditions  of  experimentation  these  figures 
are  wonderfully  alike,  and,  if  confirmed,  will  rank  with  the 
great  achievements  in  the  study  of  metabohsm. 

Regarding  cane  sugar,  the  experiment  shows  that  after  its 
ingestion  to  the  extent  of  providing  86.41  per  cent  of  the  starva- 
tion requirement  for  energy,  the  metabolism  increased  only  5 
per  cent.  It  may  be  calculated  that  if  100  per  cent,  of  the  basal 
requirement  had  been  given  the  increase  would  have  been  5.8 
per  cent. 

Summarizing,  it  is  evident  that  if  the  same  quantity  of  energy 
be  contained  in  the  ingested  food  as  the  body  requires  in  starva- 
tion at  a  temperature  of  ^t,°  C,  there  will  be  the  following 
increases  in  heat  production: 

Proteid 30.9  per  cent. 

Fat 12.7  per  cent. 

Cane  sugar 5.8  per  cent. 

The  basal  requirement  in  starvation  at  the  temperature  of 
33°  cannot  therefore  maintain  the  body  in  calorific  equilibrium. 
Rubner,  however,  calculates  the  following  as  the  minima  of 
ingestion  for  the  three  foodstuffs,  when  the  hunger  minimum  is 
100: 


138  SCIENCE   OF   NUTRITION. 

Hunger  minimum 100 

Proteid         "        140.2 

Fat  "        114.5 

Cane  sugar  minimum 106.4 

In  Other  words,  if  loo  calories  be  the  starvation  requirement, 
140  calories  must  be  supplied  if  calorific  equilibrium  is  to  be 
maintained  by  the  ingestion  of  proteid  alone;  whereas  in  the  case 
of  sugar,  106.4  calories  are  all  that  are  required  to  prevent  the 
loss  of  energy  content  from  the  body's  material.  That  these 
results  are  not  limited  in  their  application  is  shown  by  Rubner's  * 
experiment  on  a  man  who  was  given  1 20  per  cent,  of  the  starva- 
tion requirement  of  energy  first  in  the  form  of  sugar  and  then 
of  meat.     The  metabolism  was  as  follows: 

Stan'ation 2042  calories  in  24  hours. 

Sugar  alone 2087         "        "    "      " 

Meat  alone 2566        "        "    "      " 

As  neither  man  nor  dog  ever  lives  on  meat  alone  except  under 
forced  feeding,  the  results  are  not  usually  so  pronounced  as  in  the 
above  case.  Average  dietaries,  according  to  Rubner'  show 
the  following  distribution  of  percentage  of  calories: 

PERCENTAGE  OF  CALORIES  IN  DIFFERENT  DIETS. 

Proteip.  Fat.  Carbohydrates. 

I. — Well-to-do  individual iq.2  29.8  51.0 

II. — Workman 16.7  16.3  66.Q 

III. — Extreme  cases  (poverty,  etc.)  8.3  38.7  52.8 

It  is  possible  to  calculate  the  specific  dynamic  effect  of  such 
diets  by  multiplying  the  foodstuffs  by  their  specific  dynamic 
factor, — for  example,  100  per  cent,  of  proteid  =30.9  per  cent, 
increase;  i  per  cent.  =  0.309  per  cent,  increase,  and  therefore 
19.2  per  cent,  proteid  in  the  food  must  cause  an  increase  of 
0.309 X  19.2  =  5.93  per  cent,  in  the  metabolism  due  to  the  inges- 
tion of  proteid  in  Diet  I. 

Calculating  the  diets  as  above,  the  following  figures  are 
obtained : 

'  Rubner:  "Energiegesetze,"  p.  410. 
'  Rubner:  Ibid.,  p.  415. 


SPECIFIC   DYNAMIC    ACTION   OF    FOODSTUFFS.  1 39 

I.     Proteid 19.2  X  0.309  =  5.93 

Fat 29.8  X  0.127  =  3-77 

Carbohydrate 51.0  X  0.058  =  2.96 

+  12.66  per  cent. 

II.     Proteid 16.7  X  0.309  =  5.15 

Fat 16.3  X  0.127  =  2.06 

Carbohydrate 66.9X0.058  =  3.88 

+  11.09  per  cent. 

III.     Proteid 8.3  X  0.309  =  2.56 

Fat 38.7  X  0.127  =  4-91 

Carbohydrate 52.8  X  0.058  =  3.06 

+  10.53  P^r  cent. 

Thus,  if  the  starvation  requirement  for  energy  be  ingested 
the  increase  in  metabolism  would  be: 

Diet     I..: 12.66  per  cent. 

"      II 11.09 

"   III 10.52 

and  from  this  it  may  be  calculated  that  calorific  equihbrium 
would  be  reached  by  ingesting  the  following  increases  above  the 
starvation  requirement: 

Diet      1 14.4  per  cent. 

"       II 12.4 

"     III II. I         " 

On  an  average  mixed  diet  the  ingestion  minimum  is  therefore 
between  ii.i  and  14.4  per  cent,  above  the  starvation  requirement. 
This  would  be  the  maintenance  requirement.     (Rubner.) 

Should  the  fasting  metabolism  of  a  man  be  2400  calories, 
the  ingestion  of  food  would  act  as  follows : 


Diet  I. 

Diet  IH. 

(ig.25i  proteid) 

(8 

.3fJ  proteid) 

After  ingestion  of  starvation 

requirement  of  energy. .  -  -2703 

2652 

After   ingestion    of    mainte- 

nance mmimum 2745 

2666 

That   mixtures   of  the  foodstuffs  do  act  nearly  after  this 
fashion  Rubner  has  proved. 

On  account  of  the  great  specific  dynamic  action  of  proteid, 


140  SCIENCE    OF   NUTRITION. 

Rubner  would  restrict  its  use  in  fever  and  substitute  carbohy- 
drates as  the  source  of  energy. 

During  the  heated  term  of  midsummer,  decreased  proteid 
ingestion  will  materially  improve  the  personal  comfort  by  de- 
creasing the  heat  production  and  the  consequent  necessity  for 
sweat  production  (p.  183). 

As  to  the  cause  of  the  specific  dynamic  action,  Rubner  offers 
this  explanation:  The  cells  of  an  organism  require  a  fixed 
quantity  of  potential  energy  which  must  be  furnished  to  them 
in  metabolizable  compounds.  This  quantity  is  the  same  for  all 
temperatures  and  free  heat  cannot  be  employed  for  this  purpose. 
The  value  of  the  foodstuffs  depends  upon  the  potential  energy 
they  can  give  to  the  cells.  If  cane  sugar  is  ingested,  for  example, 
3.1  per  cent,  of  its  energy  is  dissipated  as  heat  when  it  is  inverted 
into  levulose  and  dextrose.  This  heat  cannot  be  used  for  the 
life  processes  in  the  cells.  When  proteid  breaks  up  in  metabo- 
lism, large  quantities  of  sugar  are  produced.  According  to 
Rubner,  this  earlier  metabolism  of  proteid  yields  heat,  but  not 
energy  for  the  cells.  He  thinks  that  the  proteid  sugar  and  pos- 
sibly other  cleavage  compounds  may  in  this  case  be  the  true 
source  of  power  for  the  living  mechanism.  The  extra  heat  of 
the  earlier  process  which  is  wasted  when  the  environment  has 
a  temperature  of  t,^°,  may  however  be  used  as  a  substitute  in 
the  place  of  the  heat,  which  may  be  required  by  chemical  regu- 
lation. Here  heat  and  not  potential  energy  is  required.  Bear- 
ing these  considerations  in  mind,  foodstuffs  are  replaceable  in  ac- 
cordance with  their  specific  respective  equivalents. 

The  theory  may  be  schematically  indicated  as  follows: 

Starvation  Requirement  of  Potential  Energy  by  Cells=ioo  Calories. 
140  Calories  in  Proteid  Meat  Ingested. 

40  Calories  =  free  heat  liber-  loo  Calories  =   Potential  en- 

ated  in  early  cleavage,  avail-  ergy  from  proteid  available 

able  in  replacement  of  heat  for  cell  life, 
of  chemical  regulation. 

From  this  it  may  be  calculated  that  when  proteid  is  metabol- 
ized 71.4  per  cent,  of  its  energy  content  is  available  for  cell  life, 


«» 


SPECIFIC   DYNAMIC    ACTION   OF   FOODSTUFFS.  I4I 

while  28.6  per  cent,  is  liberated  as  free  heat.  It  has  been  already 
shown  that  52.5  per  cent,  of  the  energy  contained  in  meat  proteid 
may  be  liberated  in  dextrose  in  the  organism  (see  p.  113),  and 
this  may  be  directly  used  by  the  cells.  The  balance  of  the  71.4 
per  cent,  of  the  directly  available  energy  (=a  residual  19  per 
cent.)  is  furnished  by  unknown  compounds.  As  regards  the 
source  of  the  free  heat  the  writer  beheves  that  it  may  be  largely 
derived  from  the  denitrogenization  of  the  amino  cleavage  prod- 
ucts of  proteid  metaboHsm.  If  one  considers  the  case  of 
alanin,  which  is  known  to  be  converted  into  lactic  acid  and  am- 
monia by  hydrolysis  in  the  organism  (p.  232),  it  is  found  that 
one  gram  of  alanin  with  a  calorific  value  of  4372,  is  almost  ex- 
actly converted  in  one  gram  of  lactic  acid  with  a  calorific  value 
of  3661^  (Berthelot).  Here  occurs  a  loss  of  heat  equal  to  16 
per  cent.  The  energy  of  lactic  acid  may  be  used  by  the  cells 
either  directly  or  through  the  conversion  into  dextrose  (see  p.  247), 
but  it  is  quite  conceivable  that  the  heat  liberated  in  its  produc- 
tion from  alanin  cannot  be  so  used.  This  elementary  example 
would  serve  to  explain  the  principle  of  the  specific  dynamic 
action  of  proteid  in  the  light  of  most  recent  knowledge.  It 
may  also  be  possible  that  such  a  cleavage  as  that  when  leucin  is 
converted  into  acetone  and  alanin  (p.  232)  may  liberate  free  heat 
of  similar  physiological  value  to  the  above. 

'•  Dr.  F.  G.  Benedict  very  kindly  sends  me  infonnation  from  which  a 
calorific  value  of  3608  may  be  calculated  for  i  gram  of  lactic  acid  present  in 
the  commercial  product. 


CHAPTER  VII. 

THE  INFLUENCE  OF  THE  INGESTION  OF  FAT  AND 
CARBOHYDRATE. 

In  a  previous  chapter  it  was  shown  that  the  amount  of  fat 
in  the  fasting  organism  materially  affected  the  amount  of  proteid 
burned.  Where  there  was  much  fat  present  Httle  proteid  was 
consumed;  where  there  was  little  fat,  much  proteid  burned; 
and  where  there  was  no  fat,  proteid  alone  yielded  the  energy 
necessary  for  life. 

The  ingestion  of  fat  alone  will  not  prevent  the  death  of  the 
organism  because  there  is  a  continual  loss  of  tissue  proteid  from 
the  body,  which  finally  weakens  some  vital  organ  to  such  an 
extent  that  death  takes  place. 

In  a  fasting  animal  which  still  contained  fat,  Voit  ^  found  that 
the  ingestion  of  loo,  200,  and  300  grams  of  fat  scarcely  influenced 
the  proteid  metabolism.  The  latter  was  slightly  increased,  if 
anything.     Voit's  table  is  as  follows: 

Fat.             Urea.  Fat.            Urea. 

o 1 1.9  300 12.0 

c 12.0  o 1 1.9 

100 12.0  o 1 1.3 

200 12.4 

To  another  dog  which  in  starvation  burned  96  grams  of  fat, 
100  grams  were  given  with  the  result  that  he  then  burned  97 
grams.  The  conditions  of  the  metaboHsm  in  both  cases  were 
therefore  identical.  The  fat  ingested  simply  burned  instead  of 
the  body's  fat,  but  the  total  amount  of  proteid  and  fat  burned 
remained  the  same.  Only  on  giving  large  quantities  of  fat 
were  both  fat  and  proteid  metabolism  increased. 

One  reason  why  the  ingestion  of  fat  up  to  the  requirement 
does  not  alter  the  metabolism  may  be  found  in  the  observation 

'  Voit:  "Physiologic  des  Stoffwechsels  und  der  Ernahrung,"  1881,  p.  128. 

142 


INFLUENCE    OF   INGESTION    OF    FAT   AND    CARBOHYDRATE.  1 43 

of  Schulz  ^  that  in  starvation  there  is  an  increase  in  the  quantity 
of  fat  in  the  blood,  and  of  Rosenfeld^  that  the  amount  of  fat  in 
the  liver  increases.  He  finds  that  a  fasting  liver  contains  lo  per 
cent,  of  fat.  If  carbohydrates  or  proteid  (which  yields  car- 
bohydrate in  metabolism)  be  ingested,  the  fat  content  falls  to 
6.2  per  cent.  If  fat  be  given  to  a  fasting  dog,  the  liver  may 
contain  25  per  cent,  of  fat;  but  if  carbohydrates  are  ingested  at 
the  same  time,  the  liver  does  not  retain  the  fat,  which  must  be 
deposited  elsewhere.  Thus,  in  the  liver  there  is  an  antagonism 
between  glycogen  deposit,  which  follows  carbohydrate  ingestion, 
and  fat  deposition. 

Meischer  found  fat  globules  in  the  muscle  cells  of  salmon 
after  their  five  to  fifteen  months'  fast  in  fresh  water,  during 
which  time  they  had  laid  their  eggs.  It  is  undoubted  that  the 
deposits  of  fat  in  the  adipose  tissue  of  these  fish  are  drawn  on  in 
starvation,  and  that  the  blood  then  carries  to  the  hungry  cells  all 
the  fat  they  require  for  their  continued  function.  It  seems 
that  the  fat  supply  to  the  cells  is  regulated  by  the  quantity  of 
other  foods  available,  and  that  even  in  starvation  there  is  at 
first  ample  fat  to  meet  the  requirement  of  the  organism.  These 
are  important  principles  which  will  be  further  discussed  when  the 
subject  of  fatty  infiltration  is  considered.  (See  Chapter  on 
Diabetes). 

As  explained  in  Chapter  VI,  the  small  increase  in  metabo- 
lism after  the  ingestion  of  fat  above  the  requirement  has  led 
Rubner^  to  determine  accurately  its  specific  dynamic  action. 
The  metabolism  does  not  rise  so  greatly  after  the  ingestion  of 
fat  as  it  does  on  a  proteid  diet.  If  the  hunger  minimum  of  calo- 
ries at  T,T,°  be  100,  then  114.5  calories  must  be  ingested  in  fat  if 
a  maintenance  diet  is  to  be  given.  This  energy  requirement  is 
140.2  in  the  case  of  proteid  diet.  Proteid  therefore  causes  a  much 
higher  heat  production  than  does  fat.  The  influence  of  external 
temperature  on  the  heat  production  after  ingesting  fat  above 

'  Schulz:  "Pfliiger's  Archiv,"  iSg6,  Bd.  Ixv,  p.  299. 

^  Rosenfeld:  "Ergebnisse  der  Physiologic,"  1903,  Bd.  ii,  I,  p.  86. 

^  Rubner:  "Energiegesetze,"  1902,  p.  353. 


144  SCIENCE   OF  NUTRITION. 

the  requirement  is  similar  to  that  after  meat  ingestion,  only  not 
so  pronounced.  Rubner^  gives  the  following  table,  showing  the 
effect  of  the  ingestion  of  17 1.3  calories  in  fat  per  kilogram  of  dog: 

SPECIFIC  DYNAMIC  ACTION  OF  FAT. 
171,3  calories  in  fat  per  kg.  dog  were  ingested. 
Calories  per  Kilo. 
Temperature.  Starvation.     After  Fat  Ingestion.  Increase. 

2.7° 152-1  155-5  +2.2percent. 

15-5° 83-1  93-4  +12.4 

31-0° 64.5  79.9  +23.9 

At  2.7°  the  excess  ingested  above  the  requirement  amounted 
to  12.6  per  cent.,  and  the  increase  in  heat  production  was  2.2 
per  cent. 

At  31°  the  excess  of  food  calories  above  the  requirement  was 
165  per  cent,  and  the  increase  in  heat  production  was  23.9  per 
cent.  In  this  instance  100  per  cent,  of  the  requirement  may  be 
calculated  to  raise  the  metabolism  14.4  per  cent,  at  a  tempera- 
ture of  31°.  This  represents  the  specific  dynamic  effect  of  fat 
on  the  metabolism.  As  in  the  cases  of  the  other  foodstuffs, 
this  action  is  to  be  explained  by  a  production  of  heat  in  early 
cleavage  processes  which  is  not  directly  available  for  the  cells 
of  the  organism. 

It  has  already  been  demonstrated  that  less  protcid  is  burned 
in  starvation  when  the  body  is  fat  than  when  it  is  lean.  It 
would  therefore  seem  that  if  proteid  and  fat  were  ingested  to- 
gether, a  similar  reduction  in  the  amount  of  the  proteid  require- 
ment would  be  effected  (Voit). 

It  has  been  shown  in  a  previous  chapter  that  nitrogenous 
equilibrium  can  be  maintained  in  a  dog  only  after  the  ingestion 
of  three  and  a  half  times  the  quantity  of  proteid  destroyed  in 
starvation  (see  p.  100). 

E.  Voit  and  Korkunoff,^  continuing  these  experiments,  find 
that  if  fat  and  meat  be  ingested  together,  the  quantity  of  the 
former  necessary  to  establish  nitrogenous  equilibrium  is  reduced 
to  between  1.6  to  2.1  times  the  starvation  minimum.     Aluch 

'  Rubner:  "Energiegesetze,"  1902.  p.  119. 

^  Voit  and  Korkunoff:  "Zeitschrift  fiir  Biologic,"  1S95,  Bd.  xxxii,  p.  117. 


INFLUENCE  OF  INGESTION  OF  FAT  AND  CARBOHYDRATE.  I45 


less  proteid  food  is  therefore  required  to  maintain  the  body's 
proteid  when  it  is  ingested  with  fat  than  when  it  is  given  alone. 
In  consequence  of  this,  proteid  is  more  readily  added  to  the 
body  when  fat  is  ingested  with  it,  as  is  seen  in  the  following  ex- 
periment of  Rubner^  on  a  man. 

INFLUENCE  OF  FAT  INGESTION  ON  NITROGEN  RETENTION. 


Food. 

N.  Metabolism. 

N. 

Fat. 

Carbohydrates. 

N  IN  Excreta. 

X  TO  Body. 

23.6 

23-5 
23.0 

23-4 

99. 

195- 
214. 

350- 

260 
226 

221 
234 

26.36 

21-55 

18.5 

17.6 

-3-64 
+  1.S1 

+4-13 

+  5-75 

With  increasing  quantities  of  fat  there  is  an  increasing 
addition  of  proteid  to  the  body. 

It  has  already  been  shown  that  proteid  ingested  alone  in  large 
quantity  establishes  nitrogen  equilibrium  at  a  higher  level, 
constantly  raising  the  amount  of  heat  produced  until  nitrogenous 
equihbriumis  reached  (the  secondary  dynamic  rise,  p.  128). 

The  same  destruction  of  the  easily  burned  proteid  takes 
place  when  it  is  given  with  fat,  as  was  shown  by  Voit  ^  in  the 
following  experiment  on  a  dog: 

THE    "SECONDARY    RISE"    IN    PROTEID    METABOLISM    ON    A 


Food. 


MEAT-FAT  DIET. 

(Weights  in 

Krams.) 

F.AT. 

Urea. 

0 

127.9 

0 

127.6 

250 

I17.9 

250 

II3-5 

250 

120.7 

250 

II5-7 

250 

119. 7 

250 

127-5 

250 

130.0 

Meat. 
1800 
1800 
1800 
1800 
1800 
1800 
1800 
1800 
1800 


^  Rubner:   Von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1903,  Bd. 
i.  P-  43- 

^  Voit:  Hermann's  Handbuch,  "Physiologie  des  Stoffwechsels,"  iSSi,  p.  131. 
10 


Flesh  to 

Body 

26 

26 

162 

171 

1 

164 

\ 
/ 

II 

146  SCIENCE   OF   NUTRITION. 

A  prolonged  deposition  of  protcid  in  the  normal  adult,  even 
when  fat  is  given  with  it,  is  demonstrably  impossible. 

The  question  arises,  does  the  ingestion  of  large  quantities  of 
fat  also  cause  an  increase  in  the  metaboUsm  until  fat  combustion 
is  balanced  by  its  ingestion? 

Rubner^  has  shown  that  this  is  not  the  case.  He  cites  the 
record  of  the  following  long  respiration  experiment  on  a  dog 
which  was  given  80  grams  of  meat  and  30  grams  of  fat  daily: 

ABSENCE  OF  THE  "SECONDARY  DYNAMIC  RISE"  IN  FAT  METAB- 
OLISM ON  A  MEAT-FAT  DIET. 


(F'at  being  given  in  excess  of  the 

requirement.) 

Calories  of  Metabolism. 

Proteid 

Fat. 

Total. 

97.2 

173.0 

270.0 

83.0 

178.0 

261. 1 

89-3 

173-5 

262.7 

85.6 

163.2 

248.9 

87.8 

169.0 

256.8 

83.0 

159.6 

242.6 

74-4 

171.7 

246.2 

78.0 

178.4 

256.3 

80.0 

179.6 

2597 

The  diet  was  58.7  per  cent,  above  the  starvation  requirement. 
It  contained  354  calories  of  which  21.5  per  cent,  were  in  proteid. 
The  mean  heat  production  during  the  period  of  ingestion  of 
food  was  256.0  calories,  and  in  the  following  starvation  days 
223.2  calories,  showing  an  increase  in  metaboHsm  of  11.2  per 
cent,  caused  by  an  excess  in  food  of  58.7  per  cent.  During 
the  later  days  the  animal  was  in  nitrogenous  equilibrium. 
Notwithstanding  an  excess  of  fat  in  the  diet,  and  a  continued 
deposit  of  fat  in  the  body,  there  was  no  increase  in  the  metabo- 
lism during  the  time  of  experimentation.  The  secondary  dy- 
namic action  noted  by  Rubner  as  regards  proteid  does  not 
therefore  take  place  as  regards  fat.  The  storage  of  fat  in  the 
body  is  consequently  a  matter  of  comparative  ease. 

Rubner"  has  compared  the  metabolism  of  a  boy  who  was 
obese  with  that  of  his  brother  who  was  a  year  older,  but  thin. 

'  Rubner:  "Energiegesetze,"  1902,  p.  251. 

'  Rubner:  "Beitrage  zur  Ernahrung  im  Knabenalter,"  1902. 


INFLUENCE   OF  INGESTION  OF   FAT   AND   CARBOHYDRATE.  I47 

They  were  the  children  of  parents  of  hmited  means  and  would 
not  naturally  be  overfed.  The  interesting  point  of  the  experi- 
ment was  whether  obesity  was  due  to  a  reduced  metabolism 
with  the  consequent  deposition  of  fat.  Each  boy  was  given  a 
maintenance  diet,  or  one  which  balanced  his  metabolism,  with- 
out adding  or  subtracting  from  his  body  substance.  The 
general  results  are  as  follows: 

Fat  Boy.  Thin  Boy. 

Age  in  years 10  11 

Weight  in  kilograms 41  26 

Total  calories  of  metabolism. . .  1 786.1  135 2.1 

Calories  per  kilogram 43.6  52.0 

Calories  per  sq.  m.  surface 1321.  1290. 

The  comparison  shows  that  the  fat  brother  had  a  larger  total 
metabolism  than  the  thin  one,  but  the  fat  boy  also  had  the 
larger  surface.  Per  square  meter  of  surface  the  metabolism 
was  the  same.  The  gradual  increase  in  the  area  of  the  body 
caused  by  filling  out  the  fat  cells  may  therefore  increase  com- 
bustion, but  this  is  not  due  to  the  specific  action  of  the  fat  on 
metabolism  as  in  the  case  of  the  secondary  dynamic  rise  after 
proteid  ingestion,  but  rather  to  the  increase  in  the  size  of  the 
body.  Carbohydrates,  which  in  excess  are  converted  into  fat, 
must  behave  in  the  same  way. 

It  will  be  noticed  that  in  the  experiment  where  80  grams  of 
meat  and  30  grams  of  fat  were  daily  ingested,  although  the  pro- 
teid metabolism  gradually  fell,  the  fat  metaboHsm  gradually 
rose,  and  in  isodynamic  relation  to  the  fall  in  proteid.  Allowing 
for  the  difference  in  specific  dynamic  action  proteid  and  fat 
replace  each  other  in  metabohsm  in  isodynamic  quantities. 

Up  to  the  present  the  discussion  of  metabolism  has  been  con- 
fined to  the  combustion  of  proteid  and  fat  in  starvation  and  after 
their  ingestion.  There  is,  however,  another  great  class  of  food- 
stuffs which  in  man  play  a  predominant  part  in  nutrition, — the 
carbohydrates. 

Starch,  milk  sugar  and  cane  sugar  are  all  converted  into 
monosaccharids  in  the  intestinal  tract,  and  dextrose,  galactose 


148  SCIENCE   OF   NUTRITION. 

and  levulose,  formed  from  them,  have  similar  physiological 
value  in  the  cells.  All  three  are  glycogen  formers,  and  thus 
galactose  and  levulose  may  be  partly  converted  into  dextrose 
through  the  glycogen  stage. 

It  has  already  been  noted  that  starvation  greatly  reduces  the 
quantity  of  glycogen  in  the  animal  body.  If  under  these  cir- 
cumstances dextrose,  levulose,  or  galactose  be  ingested  in  con- 
siderable quantity  and  the  animal  be  killed  eight  hours  after  the 
experiment,  large  quantities  of  glycogen  are  found  stored  in 
the  liver  and  muscles.  The  amount  in  the  liver  may  be  as  high 
as  forty  per  cent,  of  the  dry  solids  of  that  organ. ^  The  quantity 
found  is  much  more  than  could  have  originated  from  the  pro- 
teid  metabolism  of  the  time.  There  is  therefore  no  doubt  that 
these  sugars  are  directly  converted  into  glycogen  through 
dehydration. 

The  quantity  of  glycogen  present  in  a  living  animal  cannot 
be  accurately  estimated.  Schondorf "  gave  seven  dogs  rich 
carbohydrate  diets  for  several  days  and  found  that  the  quantity 
of  glycogen  present  in  their  bodies  varied  between  7.59  and  37.87 
grams  per  kilogram. 

The  distribution  of  this  glycogen  in  100  grams  of  the  fresh 
tissue  varied  as  follows: 

Maximum.  Minimum. 

Liver 18.69  7-3 

Muscle 3.72  0.72 

Heart 1.32  0.104 

Bone 1.90  0.197 

Intestines i  .84  0.026 

Skin 1.68  0.09 

Brain 0.29  0.047 

Blood 0.0066  0.0016 

The  traditional  distribution  of  glycogen,  one-half  to  the  Hver 
and  one-half  to  the  rest  of  the  body,  Schondorf  shows  to  be  in- 
correct. For  100  grams  of  liver  glycogen  there  occurred  in  thef 
rest  of  the  body  the  following  amounts: 

*  Voit:  "Zeitschrift  fiir  Biologie,"  1891,  Bd.  xxviii,  p.  245. 
'  Schondorf:  "Pfliiger's  Archiv,"  1903,  Bd.  xcix,  p.  191. 


INFLUENCE   OF   INGESTION   OF   FAT   AND    CARBOHYDRATE.  1 49 
Dog       1 39S.  grams. 

n 279 

III 87 

IV 76 

V 159 

VI 355 

VII 105 

It  is  an  interesting  observation  of  Kiilz^  and  of  Jensen^  that 
an  active  organ  like  the  heart  maintains  its  normal  glycogen 
content  even  after  fifteen  days  of  starvation. 

In  the  various  discussions  on  the  subject  of  glycogen  it  has 
been  shown  that  in  starvation,  and  after  proteid  and  sugar  in- 
gestion, there  is  glycogen  present  in  the  body, — a  constant 
supply  always  ready  for  emergencies,  which  can  be  reduced 
through  exercise  but  which  is  only  to  be  completely  removed 
by  tetanic  convulsions  (p.  71). 

The  writer  has  here  avoided  the  discussion  of  a  production 
of  sugar  from  fat.  To  his  mind  the  evidence  is  negative,  as 
will  be  demonstrated  in  the  Chapter  on  Diabetes. 

If  carbohydrates  be  ingested  alone  immediately  after  star- 
vation the  proteid  metabohsm  may  fall  below  the  starvation 
amount.  This  appears  in  the  experiments  of  Voit^  who  gave 
a  fasting  dog  500  grams  and  noticed  a  fall  in  proteid  metabolism 
from  181  to  170  grams. 

Rubner*  was  able  to  reduce  the  nitrogen  in  the  urine  of  a 
fasting  man  from  11.9  to  6.3  grams,  or  nearly  one-half,  by 
causing  the  subject  to  ingest  carbohydrates  alone. 

This  higher  proteid-sparing  property  gives  to  dogs  fed  on 
carbohydrates  alone  a  longer  lease  of  hfe  than  those  fed  on  fat 
alone,  although  the  ultimate  outcome  is  the  same. 

The  effect  of  feeding  with  easily  absorbable  sugar  in  excess 
is  shown  in  the  following  experiment  of  Rubner^  on  a  dog: 

'  Kiilz:  "Festschrift  zu  Ludwig,"  1891,  p.  109. 

^  Jensen:  "Zeitschrift  fiir  physiologische  Chemie,"  1902,  Bd.  xxxv,  p.  525. 

'  Voit:  Hermann's  Handbuch,  "  Stoffwechsel,"  1881,  p.  140. 

^  Rubner:  von  Leyden's  Handbuch,  1903,  vol.  i,  p.  44. 

^  Rubner:  "Die  Gesetze  des  Energieverbrauchs,"  1902,  p.  341. 


150  SCIENCE   OF   NUTRITION. 

INFLUENCE  OF  CANE  SUGAR  ON  THE  METABOLISM  OF  A  DOG. 


Food. 


Starvation 

Starvation 

85  grams  cane  sugar 
no      " 
no      " 
120      "         " 
Starvation 


N  IN  Ex- 
creta  IN 
Grams. 


1.92 
1.82 
0.91 
0.72 
0.56 

0-53 
0.69 


C    Retained 
FROM  Carbo- 
hydrates  IN 
Grams. 


10.18 

17.81 

17.61 

6.70 


Cal. 

FROM 

Proteid. 


48.0 

45-5 
22.7 
18.0 
14.0 
13.2 
17.2 


Cal.    from 
Fat  or  Car- 
bohydrates. 

203.4 
208.0 

224.4 

245-9 

247.7 

208.8 

Calories, 
Total. 


251-4 
253-0 
247.1 
263.9 
261.7 

226.0 


The  proteid  metabolism  may  thus  be  reduced  to  one-third 
the  fasting  value,  a  result  also  obtained  by  Landergren^  and 
by  Folin^  in  man. 

The  quantity  of  sugar  utilized  by  Rubner's  dog  was  35.7  to 
80.6  per  cent,  above  the  starvation  requirement  for  energy  (the 
cane  sugar  eliminated  in  the  urine  was  deducted  from  that 
ingested,  in  order  to  determine  the  quantity  utiHzed).  The 
experiment  was  done  at  33°,  and  the  specific  dynamic  action  of 
the  cane  sugar  may  be  calculated  as  raising  the  metaboHsm  5.36 
per  cent,  on  an  average. 

This  experiment  illustrates  the  ready  retention  of  carbo- 
hydrate carbon  in  the  body.  It  is  well  known  that  such  carbon 
may  be  stored  in  the  body  as  glycogen,  but  its  retention  often 
exceeds  the  animal's  abihty  to  hold  glycogen. 

Voit,  when  he  wrote  his  "Physiologie  des  Gesammt  StoflF- 
wechsels  und  der  Ernahrung,"  in  1881,  was  unable  to  give 
definite  proofs  of  the  conversion  of  carbohydrate  into  fat  in 
the  organism,  although  such  conversion  was  popularly  believed 
to  tak:  place. 

Definite  proof  of  the  conversion  of  carbohydrates  into  fat 
was  afforded  by  Meissl  and  Strohmer^  who  gave  a  pig,  weighing 
140  kilos,  two  kilograms  of  rice  daily,  and  collected  the  carbon 

*  Landergren:  "Skan.  Archiv  fiir  Physiologic,"  1903,  Bd.  xiv,  p.  112. 

*  Folin:  "American  Journal  of  Physiology,"  1905,  vol.  xiii,  p.  45. 

'  Meissl  and  Strohmer:  "  Sitzungsberichte  der  k.  Acad.  d.  Wissenschaften," 
1883,  Bd.  Ixxxviii,  III  Abtheilung. 


INFLUENCE  OF  INGESTION  OF  FAT  AND  CARBOHYDRATE.  151 

and  nitrogen  of  the  excreta  by  means  of  a  Pettenkofer-Voit 
apparatus.     The  results  were  as  follows: 

Carbon.  Nitrogen. 

Ingested  in  food 765.37  18.67 

Excreted 476.15  12.59 

Balance  retained  in  the  body. ...  289.22  6.08 

The  nitrogen  retained  represented  38  grams  of  proteid  con- 
taining 20.1  grams  of  carbon;  269.12  grams  of  retained  carbon 
were  therefore  available  for  glycogen  or  fat  construction.  Since 
the  amount  of  carbon  retained  exceeded  the  possible  glycogen 
formation,  fat  must  therefore  have  been  added  to  the  body. 
Had  all  the  carbon  retained  been  converted  into  fat  it  would 
represent  a  production  of  343.9  grams  of  fat.  This  indicates  a 
possible  conversion  of  21.5  per  cent,  of  the  starch  ingested  into 
fat. 

Similar  experiments  were  made  with  geese  by  E.  Voit  and 
C.  Lehmann.^  The  geese  were  starved  four  and  a  half  days 
and  were  then  fed  with  rice. 

One  of  these  respiration  experiments  which  lasted  thirteen 
days  has  recently  been  published  ^  and  is  as  follows : 

Nitrogen.  Carbon. 

In  the  2609  grams  of  rice 41-47  1159-7 

In  the  excreta — 

Urine  and  feces 45-39  134-8 

Respiration 657.8 

Total 45.39  792.4 

Change  in  the  body — 3.92  +  367.3 

At  the  commencement  of  the  experiment  the  animal  weighed 
4  kilograms.  There  was  no  proteid  retention,  but  31  per  cent, 
of  the  carbon  ingested  was  not  egested.  The  proteid  metabo- 
lism could  not  nearly  yield  enough  carbon  to  account  for  that 
retained.  As  the  rice  contained  but  0.51  per  cent,  of  ether  ex- 
tract the  retained  carbon  could  not  have  been  administered  in 
the  form  of  fat.     If  367.3  grams  of  carbon  had  been  retained 

*  Voit:  "  Sitzungsberichte  der  kgl.  bayr.  Acad.  d.  Wissenschaft,"  1885,  p.  288. 
^  Lehmann  and  E.  Voit:  "Zeitschrift  fur  Biologie,"  1901,  Bd.  xlii,  p.  644. 


152  SCIENCE   OF   NUTRITION. 

in  the  form  of  glycogen  this  would  have  aggregated  851  grams, 
or  twenty  per  cent,  of  the  whole  goose.  This  is  a  manifest  im- 
possibility since  E.  Voit'  found  only  2.2  per  cent,  of  glycogen 
in  a  goose  which  had  been  largely  fed  on  rice.  Since  the  carbon 
retained  could  not  have  been  stored  as  glycogen,  the  only  alter- 
native remaining  is  to  assume  its  retention  as  fat. 

Rubner  at  the  same  time  showed  the  same  principles  to  be 
tme  in  the  case  of  the  dog. 

It  is  evident,  then,  that  pigs,  geese,  and  dogs  can  convert  car- 
bohydrates into  fat.  The  fattening  of  cattle  may  be  similarly 
accomplished.  Weinland^  has  expressed  from  living  ascaris 
ferments  which  convert  glycogen  into  dextrose  and  then  into 
valerianic  and  possibly  caproic  acids, — 0.8  gram  of  dextrose 
yields  0.3  gram  of  valerianic  acid. 

This  is  suggestive  of  a  widespread  biological  capability. 

When  carbohydrates  are  converted  into  fat  in  the  organism 
the  respiratory  quotient  (voiumlo^'^"  see  p.  27),  may  rise  very 
considerably  above  unity.  This  is  for  the  reason  that  an 
oxygen  rich  substance  like  dextrose  is  being  converted  into 
substance  which  is  poor  in  oxygen.  This  intramolecular 
oxygen  derived  from  dextrose  becomes  available  for  carbon 
dioxid  production  and  the  requirement  for  inspired  oxygen 
diminishes.  Hence  the  volume  of  expired  carbon  dioxid  may 
be  greater  than  the  volume  of  inspired  oxygen.  Max  Bleibtreu^ 
found  that  the  respiratory  quotient  of  a  goose  which  had  been 
stuffed  with  grain  was  1.33,  whereas  the  same  goose  when 
fasting  showed  a  normal  quotient  for  that  condition  of  0.728. 
Pembrey*  describes  how  marmots  previous  to  the  winter  hiber- 
nation instinctively  devour  large  quantities  of  carbohydrate  food, 
and  how  the  respiratory  quotient  may  rise  even  as  high  as  1.39. 
This  indicates  a  fat  production  for  use  during  the  winter. 


'  E.  Voit:  "Zeitschrift  fiir  Biologic,"  1888,  Bd.  xxv,  p.  543. 
'  Weinland:  "Zeitschrift  fiir  Biologic,"  1901,  Bd.  xlii,  p.  55;  Bd.  xliii,  p.  86; 
1903,  Bd.  xlv,  p.  J 13. 

'  Bleibtreu:  "Pfliiger's  Archiv,"  1901,  Bd.  l.x.xxv,  p.  345. 
*Pembrey:  ''Journal  of  Physiolog}',"  1901,  vol.  xxvii,  p.  407. 


INFLUENCE    OF    INGESTION   OF    FAT   AND    CARBOHYDRATE.   1 53 

Johansson,  Billstrom  and  HeyP  have  shown  that  if  50  to  200 
grams  of  cane  sugar  be  given  a  fasting  man,  the  carbon  dioxid 
output  increases  from  22.6  grams  per  half  hour  to  about  30 
grams  per  half  hour.  The  larger  ingestion  does  not  produce 
a  higher  elimination  of  carbon  dioxid  than  does  the  smaller 
amount.  This  indicates  the  evenness  with  which  sugar  enter- 
ing the  blood- stream  is  utilized  by  the  organism.  If  sugar  be 
present  in  excess  it  may  be  stored  as  glycogen  until  it  is  needed 
by  the  cells.  The  increased  carbon  dioxid  output  does  not 
mean  increased  metabolism  in  the  sense  of  increased  heat  pro- 
duction, but  the  increase  due  to  the  destruction  of  carbohydrates 
instead  of  fat  in  the  production  of  the  same  amount  of  heat. 

The  truth  of  this  is  illustrated  by  Rubner's  ^  experiment 
on  a  man  in  which  he  compared  the  production  of  energy  in 
starvation  with  that  produced  after  the  ingestion  of  one  and 
one-fifth  that  requirement  in  the  form  of  cane  sugar.  For  the 
sake  of  emphasis  the  metabolism  after  giving  one  and  one-fifth 
the  starvation  requirement  in  the  form  of  meat  is  also  printed: 

Starvation 2042  calories. 

Sugar  (120  per  cent,  of  requirement! 2087  calories. 

Meat   (120  per  cent,  of  requirement) 2566  calories. 

It  has  been  seen  that  carbohydrates  ingested  alone  diminish 
the  proteid  metabolism.  This  reduces  the  specific  dynamic 
action  of  proteid  in  the  general  metabolism  and  the  small  specific 
dynamic  action  of  sugar  scarcely  changes  the  total  metabolism 
from  the  starvation  requirement. 

Any  excess  of  sugar  above  the  requirement  for  energy  is 
retained  in  the  body  either  in  the  form  of  glycogen  or  as  fat. 

The  contrast  given  above  between  the  results  of  the  inges- 
tion of  carbohydrates  and  of  meat  is  extremely  striking. 

It  is  evident  that  the  carbohydrate  food  protects  proteid 
tissue  from  waste  easier  than  other  foodstuffs,  and  as  a  fuel  is 
the  most  economical. 

^Johansson,  Billstrom  and  Heyl:  "Skan.  Archiv  fiir  Physiologie,"  1904, 
Bd.  xvi,  p.  263. 

^  Rubner:  "Energiegesetze,"  1902,  p.  410. 


154 


SCIENCE    OF   NUTRITION. 


When  carbohydrates  and  proteid  are  ingested  together  in 
quantity  sufficient  for  the  requirement  of  the  organism,  it  has 
been  found  that,  taking  the  starvation  proteid  metabolism  as 
one,  nitrogen  equilibrium  can  be  maintained  by  ingesting  one 
part  of  proteid/ 

The  work  of  Siven^  however  was  the  first  indication  that 
nitrogen  equilibrium  may  be  maintained  at  even  a  lower  level 
than  that  ordinarily  present  in  starvation.  A  somewhat  under- 
sized healthy  man  weighing  60  kilograms,  who  normally  ate  a 
mixed  diet  containing  16  grams  of  nitrogen,  was  given  less  and  less 
proteid  and  an  attempt  was  made  to  establish  nitrogen  equilib- 
rium at  lower  and  lower  levels.  The  daily  ration  was  rich  in 
carbohydrates  and  yielded  2444  calories.  This  must  have  been 
considerably  in  excess  of  the  requirement. 

The  experiment  was  divided  into  four  periods  of  about  a 
week  each,  which  may  be  summarized  as  follows: 


Length  in  Days. 

Days  until  N 
N  IN  THE  Food.      Equilibrium 
WAS  Obtained. 

N    LOSS  BEFORE 

N  Equilibrium 
WAS  Obtained. 

Total  N  to 
Body. 

I,   7 

II,  8 

12.69                      I 
10.40                      I 
8.71               at  once 
6.26        1            3 

0-53 
0.34 

2.09 

+9-73 
+6.04 

III,  6 

IV,  6 

+4-39 
-0.58 

It  is  apparent  that  nitrogen  equilibrium  may  be  established 
after  ingesting  6.26  grams  of  nitrogen,  although,  as  has  been 
seen,  the  elimination  during  the  early  days  of  starvation  in  man 
is  usually  10  grams.  During  the  first  three  periods  of  reduced 
proteid  intake,  as  much  as  20.16  grams  of  proteid  nitrogen  were 
actually  added  to  the  body.  In  a  fifth  period  nitrogen  equilib- 
rium was  obtained  on  the  fourth  day  on  a  diet  containing  4.52 
grams  of  nitrogen. 

The  susceptibihty  of  the  proteid  metabolism  to  sudden 
withdrawal  of  carbohydrates  was  shown  by  Lusk^  upon  himself. 
Nitrogen  equilibrium  was  nearly  established  in  two  different 

'  E.  Voit  and  Korkunoff :  Loc.  cit. 

^  Siven:  "Skan.  Archiv  fur  Physiologic,"  1900,  Bd.  x,  p.  91. 

'  Lusk:  "Zeitschrift  fiir  Biologic,"  1890,  Bd.  xxvii,  p.  459. 


INFLUENCE    OF   INGESTION   OF   FAT    AND    CARBOHYDRATE.   1 55 

experiments  at  different  levels  with  the  ingestion  of  20.55  ^^^1 
9.23  grams  of  nitrogen  respectively.  In  the  first  experiment 
withdrawal  of  350  grams  of  carbohydrates  from  the  mixed  diet 
caused  a  rise  in  nitrogen  metabolism  from  ig.84  to  27.00  grams, 
incurring  a  loss  of  body  nitrogen  of  6.45  grams.  In  the  second 
experiment  withdrawal  of  the  carbohydrates  increased  the  nitro- 
gen excretion  from  11.44  to  17.18,  a  loss  to  the  body  of  7.95 
grams.  The  losses  are  for  the  second  day  after  the  withdrawal 
of  the  carbohydrates,  since  the  metabolism  remains  under  the 
influence  of  the  glycogen  supply  during  the  first  day. 

Subsequent  experimentation  has  showm  that  partial  re- 
placement of  carbohydrates  by  fat  in  the  diet  may  have  no  in- 
fluence, or  only  a  transitory  one,  upon  the  amount  of  proteid 
metabolized.  This  is  of  value  in  practical  dietetics.  Tallquist^ 
established  nitrogen  equihbrium  in  a  man  with  a  diet  containing 
about  16  grams  of  nitrogen,  10  per  cent,  of  the  calorific  value 
being  contained  in  proteid  and  90  per  cent,  in  carbohydrates.  On 
replacing  one-third  of  the  carbohydrate  calories  in  the  diet 
with  fat  calories  an  increased  proteid  metaboHsm  was  observed 
for  two  days,  followed  by  nitrogen  equilibrium  on  the  third  day. 
The  food  given  contained  35  calories  per  kilogram,  a  moderate 
quantity,  and  was  made  up  as  follows: 

Period  I.  16.27  g-  N  4-     44-6  g.  Fat  -1-  466  g.  Carb.    =  2866  Cal. 
"     II.  16.08  g.  N  -\-  140. 1  g.  Fat  -I-  250  g.  Carb.   =  2873  Cal. 

The  nitrogen  ehmination  was  as  follows: 

Day.  N   Excreted.  N  Balance. 

Period    I. — i 17. 11  — 0.84 

2 14.40  -I- 1.86 

3 14-65  +1.62 

4 15-58  -1-0.69 

"       11.-5 17-66  —1.58 

6 17-32  —12.4 

7 15-94  4-0.14 

8 16.22  — 0.14 

This  proves  that  with  a  diet  containing  16  grams  of  nitrogen 
in  proteid,  nitrogen  equilibrium  is  about  as  easily  maintained 
on  a  mixed  diet,  including  carbohydrates  and  fats,  as  when  only 
carbohydrates  are  allowed  with  the  proteid. 

'  Tallquist:  "Archivfiir  Hygiene,"  1902,  Bd.  xli,  p.  177. 


156  SCIENCE    OF   NUTRITION. 

Similar  principles  have  been  beautifully  illustrated  by  Lan- 
dergren/  Diets  containing  carbohydrates  and  fats  but  scarcely 
any  nitrogen  (about  one  gram  daily),  were  given  men  and  the  pro- 
teid  metabolism  noted.  This  condition  is  called  that  of  specific 
nitrogen  hunger.  After  four  days'  administration  of  such  a  diet 
the  urinary  nitrogen  may  be  reduced  to  less  than  four  grams. 

In  one  experiment  in  which  this  was  accomplished  car- 
bohydrates were  entirely  replaced  by  fat  with  the  result  that 
proteid  metabolism  rose  to  the  amount  found  in  starvation 
(about  10  grams).  It  has  already  been  explained  that  inges- 
tion of  fat  alone  will  not  affect  proteid  metabohsm  in  starvation. 
The  experiment  is  as  follows: 

Carbohydrate  Period.  Fat  Period. 

Diet   =   45.2  Cal.  per  Kg.  Diet   =   43.7  Cal.  per  Kg. 

X  in  Urine.  N  in  Urine. 

Davo *  12.76  Dav  5 4.28 

"■  I "'   6 S.86 

"    2 "     7 9-64 


3 

"    4 3-76 

*  Ordinary  diet. 

On  day  5,  the  first  of  the  fat  diet,  it  is  evident  that  the  pro- 
teid metabolism  was  affected  by  the  use  of  the  glycogen  supply 
of  the  body,  an  influence  which  became  negligible  on  the  second 
and  third  days  of  the  fat  diet  (p.  53). 

Landergren  gives  the  following  results  in  various  cases  of 
specific  nitrogen  hunger,  showing  the  nitrogen  in  the  urine 
before  the  diet,  and  after  four  days  thereof: 

II.        in.      IV.        V. 

N  in  urine  (ordinary   diet) 12.76     11.87     13.7       15.2 

N  in  urine  (specific  N  hunger 3.76       3.95       3.04       4.2 

Calories  in  diet  per  kg 45.2       ^7.8       45.0       38.4 

This  reduction  of  proteid  metabolism  to  four  grams  on  the 
fourth  day  was  brought  about  by  the  following  diets  in  the  dif- 
ferent cases: 

I^-   75°  g-  carbohydrates =  45.2  cal.  per  kg. 

III.  300  g.  carbohydrates  -1- 150  g.  fat.=  37.8    "       "     " 
V.  380  g.  carbohydrates  -t- 150  "     "    =  38.4    "       "     " 

'  Landergren:  "Skan.  .Archiv  fiir  Physiologie,"  1903,  Bd.  xiv,  p.  112. 


INFLUENCE   OF   INGESTION   OF    FAT    AND    CARBOHYDRATE.   1 57 

A  diet  containing  half  its  calories  in  carbohydrates  and  half 
in  fat  has  therefore  the  same  proteid  protecting  power  as  one 
made  up  of  carbohydrates  alone.  This  demonstrates  the 
rationahty  of  a  mixture  of  the  non-nitrogenous  foodstuffs. 

Landergren  finds  that  on  a  diet  containing  two- thirds  of  the 
calorific  requirement  the  urinary  nitrogen  on  the  fourth  day 
may  be  eight  grams,  or  nearly  the  fasting  quantity.  The  diet 
was  made  up  of — 

X.  240  g.  carbohydrate  -f  64  g.  fat =21.8  cal.  per  kg. 

Therefore,  in  specific  nitrogen  hunger  with  undernutrition,  the 
nitrogen  ehminated  in  the  urine  appears  to  be  increased.  It  is 
a  pity  that  this  statement  rests  on  only  one  experiment,  for  it 
does  not  appear  in  accord  with  the  following  work  of  Chittenden. 

Chittenden^  finds  that  nitrogen  equilibrium  may  be  main- 
tained on  a  diet  containing  a  very  small  amount  of  proteid  and 
two-thirds  of  the  body's  requirement  of  energy.  The  first  ex- 
periment was  on  Fletcher  and  lasted  six  days.  The  daily  ration 
contained  7.19  g.  nitrogen  +  38.0  g.  fat  -1-  253  g.  carbohydrates = 
21.3  calories  per  kg.  The  excreta  contained  6.90  grams  of 
nitrogen  daily.  On  this  diet  the  individual  showed  ' '  remarkable 
physical  strength  and  endurance." 

Another  experiment  was  performed  by  Chittenden  on  him- 
self and  lends  itself  for  interesting  comparison  with  the  results 
of  the  ingestion  of  a  maintenance  ration.  The  food  was  prin- 
cipally vegetarian.     The  results  may  be  thus  tabulated: 

A  LOW  LEVEL  OF  NITROGEN   EQUILIBRIUM   IN   NORMAL 
AND  UNDERNUTRITION. 


Diet. 

N  Excretion. 

Date. 

N  IN  Grams. 

Cal.  per  Kg. 

N  Balance. 

March  23 

March  25 

6.79 

6.88 

34-7 
22.4 

6.56 
6.34 

-1-0.23 
+  0.54 

Nitrogen  equilibrium  may  therefore  be  maintained  at  a  low 
^Chittenden:  "Physiological  Economy  in  Nutrition,"  1904,  pp.  14,  40. 


158  SCIENCE    OF    NUTRITION. 

level  even  during  the  state  of  undernutrition  present  when  22.4 
calories  per  kilogram  are  in  the  daily  diet.  On  a  milk  diet 
Rubner^  found  that  the  ingestion  of  2483  grams  of  milk  con- 
taining 84  grams  of  proteid  and  two-thirds  the  body's  require- 
ment of  energy  resulted  in  the  addition  of  6.7  grams  of  proteid 
to  the  body  daily  for  three  days  (p.  190). 

It  is  a  valuable  piece  of  information  to  know  that  one  may 
diet  an  obese  patient  on  a  food  containing  little  proteid  and  two- 
thirds  the  body's  energy  requirement  without  danger  of  pro- 
teid loss.  The  other  third  of  the  necessary  energy  will  be  fur- 
nished by  the  body's  own  store  of  fat.  It  is  not  remarkable  that 
the  body  is  capable  of  great  physical  effort  on  such  a  diet,  for 
a  fasting  man  is  also  competent  in  this  direction  (p.  73). 

In  the  last  chapter  mention  was  made  of  the  sparing  action 
of  gelatin  on  proteid  metabolism  and  its  ingestion  was  found  to 
prevent  about  23  to  37.5  per  cent,  of  the  proteid  loss  during 
starvation.  The  sparing  might  be  greater  when  gelatin  was 
ingested  with  a  mixed  diet.  To  show  this,  J.  R.  Murlin^  has 
experimented  in  the  writer's  laboratory  on  a  man  weighing 
seventy  kilograms.  The  man  starved  three  days,  and  then  fol- 
lowed a  period  of  three  days  during  which  nitrogen  equilibrium 
was  maintained  on  a  diet  containing  the  quantity  of  nitrogen 
ehminated  during  starvation.  The  proteid  was  supplied  by 
beefsteak,  oatmeal,  and  eggs,  which,  with  cream  and  sugar, 
furnished  a  total  of  3000  calories.  Two-thirds  of  this  total 
proteid  nitrogen  was  then  replaced  by  gelatin  nitrogen  for  two 
days  and  the  calories  raised  to  3400  by  the  addition  of  cane 
sugar.  The  result  was  that  during  the  second  day  0.06  gram 
of  nitrogen  were  added  to  the  body. 

Murlin  obtained  the  same  results  on  a  dog  and  also  showed 
that  three-quarters  of  the  starvation  nitrogen  ingested  as  gelatin 
and  one-quarter  as  proteid  were  not  able  to  maintain  nitrogen 
equilibrium.     Two-thirds  the  starvation  nitrogen  requirement 

'  Rubner:   "Zeitschrift  fiir  Biologic,"  Bd.  xv,  1879,  p.  130. 
'  Murlin:   Proceedings  American  Physiological  Society,  "American  Journal 
of  Physiology,"  1905,  vol.  xiii,  p.  29. 


INFLUENCE  OF  INGESTION  OF  FAT  AND  CARBOHYDRATE.    1 59 

ingested  as  gelatin  and  one-third  as  proteid  maintain  nitrogen- 
ous equilibrium.  Carbohydrates  ingested  alone  reduce  proteid 
metabohsm  to  one-third  that  found  in  starvation.  One-third 
the  starvation  quantity  seems  to  be  the  limit  of  proteid  metabo- 
lism compatible  with  life. 

Since  carbohydrates  so  effectively  spai-e  proteid  from  com- 
bustion it  would  seem  logical  that  their  use  would  render  the 
retention  of  proteid  in  the  body  easier  than  when  fat  is  given 
with  proteid. 

Liithje^  finds  a  long  continued  nitrogen  retention  in  man 
when  much  nitrogen  in  proteid  is  ingested  (up  to  50  g.  N  daily!) 
and  carbohydrates  and  fat  making  a  total  of  4000  calories  or 
66  calories  per  kilo.     (See  also  Bornstein's  experiment,  p.  100.) 

In  a  subsequent  paper  Liithje^  finds  that  the  PgOg  retention 
in  convalescence  is  that  which  corresponds  to  the  retention  of  pro- 
teid as  new  tissue  and  for  the  upbuilding  of  the  bones.  Some- 
times in  a  healthy  person  not  enough  PjOj  is  retained  to  build 
up  "flesh,"  and  the  proteid  retained  must  therefore  exist  in  the 
form  of  "deposit  proteid."  This  proteid,  he  says,  is  not  stored 
in  the  blood,  for  the  composition  of  the  blood  does  not  alter; 
but  is  perhaps  retained  in  the  cellular  fluids,  just  as  glycogen 
is  retained  by  the  cells. 

In  conclusion,  it  may  be  said  that  carbohydrates  are  the 
most  economical  of  the  foodstuffs,  both  physiologically  and 
financially.  They  are  the  greatest  spare rs  of  proteid.  In- 
gestion of  fat  has  for  its  object  the  relieving  of  the  intestine 
from  excessive  carbohydrate  digestion  and  absorption.  Inges- 
tion of  fat  in  too  large  quantities  leads  to  digestive  disturbances 
and  if  carbohydrates  are  entirely  abandoned,  to  acetonuria. 

*  Liithje:   "Zeitschrift  fiir  klinische  Medizin,"  1902,  Bd.  xliv,  p.  22. 
^Liithje:    "Deutsches  Archiv  fiir  klinische  Medizin,"  1904,  Bd.  Ixxxi,  p. 
278. 


CHAPTER  VIII. 

THE   INFLUENCE    OF   MECHANICAL   WORK  ON 
METABOLISM.' 

The  source  of  mechanical  work  must  be  from  metabolism, 
for  mechanical  energy  cannot  be  derived  from  nothing.  The 
necessary  energy  might  be  obtained  in  one  of  two  ways,  either 
at  the  expense  of  a  proportionate  reduction  in  the  quantity  of 
heat  liberated  by  the  resting  organism,  or  by  an  increase  in  the 
amount  of  the  metabolism.  In  the  former  case  work  would 
diminish  the  heat  production,  and  might  cool  the  tissues,  which 
is  not  observed  to  take  place.  If  work  were  done  at  the  expense 
of  increased  metabolism,  and  if  this  increase  were  completely 
converted  into  mechanical  effect,  then  the  heat  production  in  the 
organism  might  remain  the  same  as  in  the  resting  state.  If, 
however,  the  result  of  mechanical  effort  be  a  stimulation  of  me- 
tabolism to  the  extent  of  not  only  enabling  the  body  to  do  work, 
but  also  causing  it  to  produce  more  heat  than  when  at  rest, 
then  the  tendency  of  the  tissues  must  be  to  grow  warmer,  per- 
haps with  a  resulting  outbreak  of  sweat  to  reduce  the  body 
temperature  through  physical  regulation.  The  last  named 
is  the  actual  process. 

Lavoisier's  discovery  that  the  absorption  of  oxygen  is  in- 
creased during  mechanical  exercise,  firmly  established  the  fact 
of  a  higher  metabolism  under  these  conditions. 

The  first  experiments  in  which  the  effect  of  work  upon  the 
total  metabolism  was  demonstrated  were  made  upon  a  man  by 
Pettenkofer  and  Voit.^     A  man  turned   an  ergostatic   wheel 

*  In  the  account  of  metabolism  during  starvation,  a  short  description  has 
already  been  given  of  the  influence  of  mechanical  work  on  proteid  metabolism, 
of  the  influence  of  posture  on  general  metabolism,  and  of  the  relation  of  the 
amount  of  metabolism  to  the  diurnal  variations  of  human  temperature. 

'  Pettenkofer  and  Voit:  "Zeitschrift  fiir  Biologic,"  1866,  Bd.  ii,  p.  538. 

160 


INFtUENCE    OF    MECHANICAL    WORK   ON    METABOLISM.     l6l 

7500  revolutions  on  each  of  the  working  days  for  a  period  of 
nine  hours,  affording  sufficient  exercise  to  cause  great  fatigue 
at  the  end  of  the  day.  The  experiments  were  made  both  during 
hunger  and  when  the  man  was  ingesting  a  medium  mixed  diet. 
The  food  suppKed  in  the  mixed  diet  contained: 

Grams.  Calories. 

Proteid 1 2 1 . 7  506 

Fat 117.  1 088 

Carbohydrates 352.  1443 

Total 3037 

The  metabolism  of  the  strong  workman,  weighing  seventy 
kilograms,  at  rest  and  at  work,  starving  or  on  the  medium  mixed 
diet  as  given  above,  is  presented  in  the  following  table  :^ 

EFFECT  OF  MECHANICAL  WORK  ON  METABOLISM  IN  MAN. 


Grams  Metabolized. 

Proteid. 

Fat. 

Car- 
bohy- 
drates. 

Cal.  of 

Metab- 
olism. 

Cal. 

ABOVE 

Fasting 
Quantity 

Experiment 
No.    OF    Pet- 
tenkofer 

AND  \'0IT. 

Starvation — Rest 

—Rest 

—Work 

70.8 
68.7 
66.1 

222 
208 
387 

2374 
2231 
3882 

1582 

I 
III 

IV 

Mixed  Diet— Rest 

—Rest 

—Rest 

-Work.... 
—Work.... 

121. 7 
118.7 
125.0 
121. 7 
122.0 

73 

93 

84 

208 

152 

352 
352 
352 
352 
352 

2638 
2714 
2750 
3856 
3378 

336 

412 

458 

1554 

1076 

V 

\T 

VII 

VIII 

IX 

From  these  early  experiments  it  was  evident  that  mechanical 
work  did  not  increase  proteid  metabolism  even  in  starvation, 

'I  have  multiplied  the  nitrogen  of  the  ingesta  and  egesta  by  6.25  to  obtain 
the  quantity  of  the  proteid  given  and  metabolized.  The  ratio  N:C  =  1:3.28 
in  proteid  has  been  employed.  The  dry  starch  has  been  calculated  as  con- 
taining 44.2  per  cent,  and  the  fat  as  containing  76.5  percent,  of  carbon,  which 
were  the  figures  used  by  Pettenkofer  and  Voit.  Rubner's  standard  calorimetric 
values  have  been  used.     (See  Introductory  Chapter.) 


1 62  SCIENCE   OF   NUTRITION. 

but  that  the  power  to  do  work  might  readily  be  supplied  l)y  the 
increased  metabolism  of  fat. 

It  is  interesting  to  note  the  increase  of  the  metabolism  above 
the  fasting  minimum  under  the  above  circumstances.  This 
relation  is  embodied  in  the  following  table: 

Calories  of  Tk^dttaci- 

Metabolism.  Increase. 

Starvation — Rest  (average) 2302 

—Work 3S82  1582 

Medium  diet — Rest  (average) 2717  415 

—Work 3856  1554 

—Work 3378  1076 

This  table  indicates  a  specific  dynamic  action  of  the  food 
amounting  to  415  calories.  Another  conclusion  may  be  drawn 
from  the  table,  and  one  which,  if  true,  is  of  importance;  it  is 
that  during  the  worMng  days  the  specific  dynamic  action  0}  the 
food  does  not  appear.  In  other  words  the  metabolism  during 
work  on  a  mixed  diet  is  not  greater  than  during  starvation  when 
the  same  amount  of  work  is  being  effected.  It  may  be  that  the 
free  heat  liberated  as  the  result  of  the  specific  dynamic  action 
of  the  food  can  be  utihzed  in  warming  the  cells  in  the  service  of 
the  production  of  mechanical  energy,  just  as  it  is  used  in  lieu 
of  the  heat  produced  through  chemical  regulation.  If  this  be 
true,  giving  protcid  to  men  at  work — for  example,  athletes — 
would  not  entail  economic  waste  of  the  fraction  usually  lost 
when  it  is  given  during  rest. 

Rubnerin  his"  Energiegesetze "  writes  that  he  is  investigating 
the  influence  of  work  on  metabolism,  and  it  may  be  assumed 
that  this  problem  has  already  been  solved.  The  writer  merely 
advances  the  above  as  a  suggestion  of  possibilities. 

Rubner*  shows  that  a  man  of  seventy  kilograms  weight, 
developing  mechanical  energy  to  the  extent  of  15,000  kilogram- 
meters  per  hour,  produces  practically  the  same  quantity  of  car- 
bon dioxid,  no  matter  what  the  temperature  of  his  environment 
may  be.     The  results  of  the  experiment  are  as  follows: 

'  Rubner:  Von  Leyden's  Handbuch,  "Die  Ernahrungstherapie,"  1903, 
Bd.  i,  p.  74. 


INFLUENCE    OF   MECHANICAL    WORK   ON   METABOLISM.     163 


Percentage 

Carbon  Dioxid 

Water  Ex- 

[PERATURE 

THE  Air. 

Moisture  in 

PER  Hour 

creted  PER  Hour 

THE  Air. 

in  Grams. 

IN  Grams. 

7-4° 

81 

84.0 

58.0 

12.7° 

84 

78.5 

70.8 

16.7° 

59 

97.0 

138.1 

17.5° 

87 

84-5 

90.4 

18.8° 

83 

81.2 

112. 8 

25.0° 

47 

78.7 

230.0 

This  person  while  at  rest  and  at  a  temperature  of  21.1°  ex- 
creted 33.6  grams  of  carbon  dioxid  and  42  grams  of  water. 

It  is  clear  that  during  work  the  metabohsm  is  independent 
of  surrounding  temperature,  of  chmatic  conditions.  In  other 
words,  during  mechanical  work  the  influence  of  the  chemical 
regulation  of  body  temperature  may  be  eliminated.  The  extra 
heat  production  in  doing  mechanical  work  is  utihzed  instead  of 
the  production  of  heat  which  is  excited  reflexly  through  cold. 

Generally  speaking,  neither  clothing  nor  temperature  affect 
the  amount  of  the  metabolism  during  exercise.  They  influence 
only  the  quantity  of  water  ehminated  in  the  perspiration,  in 
the  effort  of  the  body  to  maintain  its  normal  temperature  through 
physical  regulation.  It  is  evident  from  Rubner's  details  of  the 
water  excretion  that  at  a  low  temperature  the  extra  heat  pro- 
duction during  mechanical  exercise  is  lost  by  radiation  and 
conduction.  Rubner  explains  that  the  shght  increase  in  the 
excretion  of  water  above  that  lost  while  at  rest,  is  due  to  its 
increased  evaporation  through  increased  respiratory  activity. 
At  a  higher  temperature  conduction  and  radiation  become 
insufficient  to  cool  the  body,  and  a  large  proportion  of  the 
loss  of  heat  takes  place  at  the  expense  of  the  evaporation  of 
sweat. 

In  hot,  moist  climates,  however,  the  coohng  of  the  body 
through  the  evaporation  of  moisture  becomes  difficult,  and  this 
is  especially  pronounced  in  the  case  of  fat  people  (p.  94),  who 
with  difficulty  discharge  the  heat  produced  within  them.  Broden 
and  Wolpert  ^  show  the  effect  of  the  action  of  temperature  and 
humidity  on  the  metabohsm  of  a  fat  man,  weighing  loi  kilo- 
grams, who  executed   the  same  amount  of  mechanical  work 

'  Broden  and  Wolpert:  "  Archiv  fiir  Hygiene,"  1901,  Bd.  x.xxix,  p.  298. 


164 


SCIENCE   OF   NUTRITION. 


under  various  conditions  of  experimentation.  The  work  was 
light,  being  5375  kilogrammeters  per  hour.  The  results  were 
as  follows: 


EFFECT  OF  WORK,  TEMPERATURE,  AND  HUMIDITY  ON  THE 
METABOLISM    OF  A   FAT  INDIVIDUAL. 


Grams  per  Hour. 

Temperature. 

Dry  Air. 

Humid  Air. 

CO2   in  Grams 
per  hour. 

H2O  in  Grams 
per  hour. 

COj  in  Grams 
per  hour. 

HjO  in  Grams 
per  hour. 

20° 

47.8 
47-3 
50-3 

319  +  38  g. 
sweat. 

46.4 
48.0 
60.7 

28-30° 

36-37° 

26Q 
+ 
266  g. 
sweat. 

This  individual  was  the  same  already  mentioned,  p,  94, 
and  the  explanation  given  there  is  equally  applicable  here.  In 
a  dry  climate  the  same  amount  of  mechanical  work  may  be  ac- 
complished by  a  fat  person  at  both  20°  and  30°  without  changing 
the  metabolism.  At  a  temperature  of  37°  the  metabohsm  rises, 
for  the  cooling  power  of  the  evaporating  sweat  does  not  seem 
sufficient  to  act  through  the  dense  covering  of  fat.  This  action 
is  intensified  in  moist  air  where  the  evaporation  of  water  is 
hindered.  Under  these  latter  conditions  the  small  amount  of 
work  was  accomplished  only  at  the  expense  of  great  discomfort 
and  profuse  perspiration. 

The  obese  therefore  work  under  great  disadvantage  in  a  hot, 
and  especially  in  a  hot  and  moist,  chmate.  The  profuse  per- 
spiration explains  their  desire  for  water  to  drink. 

In  the  early  experiments  of  Pettenkofer  and  Voit,  already 
cited,  it  was  shown  that  work  did  not  raise  the  proteid  metabol- 
ism even  in  starvation,  and  that  the  source  of  the  power  ap- 
peared to  be  derived  from  the  increased  combustion  of  the 
non-nitrogenous  fat. 


INFLUENCE   OF   MECHANICAL   WORK   ON   METABOLISM.     1 65 

In  other  experiments  a  slight  rise  in  the  nitrogen  metabolism, 
.continuing  into  the  day  following  work,  has  been  noted.  The 
proteid  metabolism,  however,  is  not  sufficient  to  yield  the 
energy  necessary  for  a  hard  day's  work.  In  the  well  known 
experiments  of  Fick  and  Wislicenus  ^  the  authors  climbed  the 
Faulhorn,  in  Switzerland,  a  mountain  1956  meters  high.  The 
product  of  their  weight  into  the  height  to  which  they  raised 
themselves  gave  them  the  work  done.  The  proteid  metabohsm, 
as  calculated  from  the  nitrogen  in  the  urine  during  the  walk  and 
seven  hours  thereafter,  could  have  afforded  only  a  third  of  the 
necessary  energy  for  the  ascent  of  the  mountain.  The  experi- 
menters took  their  last  nitrogenous  food  seventeen  hours  be- 
fore starting  on  their  walk.  They  climbed  for  six  hours  and 
collected  the  urine  of  this  period  and  that  of  seven  hours  there- 
after.    Their  results  were  as  follows: 


Urinary  N 

OF  13  HRS. 

Dynamic    Value 
OF  N  IN  Kgm. 

Body 
Weight. 

Height  of  Faul- 
horn. 

Work   in 
Kgm. 

Fick 

Wislicenus  . . 

5-74 
5-54 

63.378 
61,280 

66 

76 

1956  meters. 
1956  meters. 

129,096 
148,656 

The  work  accomplished  was  far  in  excess  of  the  energy 
liberated  from  the  proteid  metabohsm  of  the  time.  The  output 
of  energy  as  measured  above  was  not  all  the  increase  in  the 
amount  of  mechanical  energy  during  the  period,  for  the  heart 
and  respiratory  muscles  acted  with  greater  force,  and  energy 
was  expended  by  swinging  the  arms  and  by  friction  on  the  road. 

The  fact  observed  by  Pettenkofer  and  Voit  that  proteid 
metabolism  may  not  be  appreciably  affected  during  mechanical 
w^ork  has  been  abundantly  confirmed  by  Knimmacher.^  A 
porter  weighing  79  kilograms  was  given  a  diet  containing  3700 
calories,  14.28  grams  of  proteid  nitrogen  and  a  large  amount 
of  carbohydrate.  The  man  turned  a  dynamometer  and  pro- 
duced 402,000  kilogrammeters  of  work.     The  shght  increase 

*  Fick  and  Wislicenus:  "  Myothermische  Untersuchungen,"  1889. 
'  Krummacher:  "Zeitschrift  fiir  Biologic,"  1896,  Bd.  xxxiii,  p.  108. 


l66  SCIENCE   OF   NUTRITION. 

in  proteid  metabolism  could  have  yielded  but  three  per  cent, 
of  the  energy  required  for  the  work.  Krummachcr  states  that 
proteid  metabolism  may  increase  during  work  only  when  the 
non-nitrogenous  fat  and  carbohydrates  become  less  available 
in  metabolism.  We  have  already  seen  that  proteid  metabolism 
rises  in  the  absence  of  carbohydrates.  It  may  be  that  with  the 
exhaustion  of  carbohydrates  during  exercise,  a  period  ensues 
when  the  loss  of  their  influence  leads  to  an  increased  proteid 
destruction.  The  larger  the  quantity  of  carbohydrate  given  the 
less  marked  would  be  this  influence.  It  is  interesting  in  this 
connection  that  soldiers  when  starting  on  a  march  may  have  a 
high  respiratory  quotient  (indicating  the  combustion  of  carbo- 
hydrates) which  falls  at  the  end  of  the  march  (fat  combustion) 
and  which  may  remain  lower  than  at  first,  even  on  a  day  fol- 
lowing the  march.^  The  fact  that  mechanical  work'  may  be  ac- 
complished at  the  expense  of  an  increased  combustion  of  fat 
and  carbohydrate  should  not  cause  one  to  forget  that  proteid  may 
become  the  sole  source  of  energy  in  the  body.  It  has  already 
been  shown  that  a  fasting  animal,  after  burning  all  his  fat,  main- 
tains his  life  on  proteid  alone  (p.  66),  and  that  Pfliiger  kept  a 
dog  in  active  condition  on  meat  alone.  As  proteid  may  yield 
58  per  cent,  of  sugar,  this  substance  may  still  be  the  principal 
source  of  energy. 

Bornstcin'  reports  continual  retention  of  ingested  proteid 
during  seventeen  days'  work,  at  a  time  when  there  was  no  fat 
retention.  The  quantity  of  proteid  given  was  large,  containing 
19.96  grams  of  N,  and  the  daily  work  accomplished  was  mod- 
erate, being  17,000  kilogrammeters.  The  nitrogen  retention 
amounted  to  1.475  grams  daily,  or  an  addition  of  800  grams  of 
"flesh"  to  the  body  in  seventeen  days. 

Loewi^  reaches  the  same  conclusion  that  long  continued 
muscular  exercise  favors  proteid  retention.  This  suggests  the 
basis  of  muscular  hypertrophy  due  to  physical  exercise. 

'  Zuntz  and  Schumburg:  "Physiologic  des  Marsches,"  igor. 
'  Bornstein:  "Pfliiger's  Archiv,"  1901,  Bd.  Ixxxiii,  p.  540. 
'  Loewi:  "Archiv  fiir  Physioiogie,"  1901,  p.  299. 


INFLUENCE    OF    MECHANICAL    WORK    ON    METABOLISM.     167 

Large  proteid  ingestion,  however,  is  not  apparently  essential  to 
the  full  maintenance  of  physical  power.  This  has  been  shown 
by  Chittenden  ^  who  maintained  soldiers  and  athletes  in  physical 
training  for  months  at  a  time  on  diets  containing  between  seven 
and  ten  grams  of  nitrogen,  or  about  half  what  the  average  man 
takes  if  the  question  be  left  to  his  taste  (see  p.  179). 

It  is  evident  that  the  power  to  accomplish  muscular  work  is 
not  usually  derived  from  proteid  metabolism,  but  from  the  com- 
bustion of  the  non-nitrogenous  sugar  and  fat. 

Therefore,  physical  exercise  requiring  fat  consumption  with- 
out concomitant  destruction  of  proteid  must  be  of  the  greatest 
value  in  the  treatment  of  obesity. 

The  problem  at  once  arises :  What  is  the  relative  value  of 
fats  and  carbohydrates  as  fuel  for  the  production  of  mechanical 
energy  by  the  body  ? 

Zuntz,^  from  experiments  made  by  Heineman,  calculates 
that  w^hen  carbohydrates  predominate  in  a  man's  diet  an 
amount  of  energy  above  the  resting  requirement  is  liberated 
which  equals  9.33  calories  for  every  kilogrammeter  of  work  ac- 
comphshed,  whereas  when  fat  is  given  10.37  calories  are  hberated 
in  the  performance  of  the  same  amount  and  the  same  kind  of 
work.  The  work  was  done  by  turning  the  wheel  of  an  ergostat. 
Since  one  kilogrammeter  is  the  mechanical  equivalent  of  2.35  cal- 
ories, it  is  evident  that  25  per  cent,  of  the  total  excess  of  energy  de- 
veloped by  work  is  convertible  into  mechanical  effect,  the  balance 
being  dissipated  as  heat.  Similar  experiments  made  by  Zuntz 
on  himself  showed  that  9.39  and  9.33  calories  of  metabohsm 
were  hberated  on  a  fat  diet,  10.37  and  10.41  on  a  carbohydrate 
diet,  when  one  kilogrammeter  of  work  was  accomplished. 

There  seems  to  be  little  difference  in  the  efficacy  of  the  body 
as  a  machine,  whether  fat  or  carbohydrates  are  used  as  fuel. 

Heineman^  remarks  that  Chauveau's  idea  that  fat  must  be 
first  converted  into  sugar  before  being  available  for  mechanical 

'  Chittenden:  "Physiological  Economy  in  Nutrition,"  1905. 
*  Zuntz:  "Pfluger's  Archiv,"  1900,  Bd.  Ixxxiii,  p.  557. 
^  Heineman:  Ibid.,  p.  476. 


l68  SCIENCE   OF   NUTRITION. 

work  can  scarcely  be  valid,  for  such  a  conversion  of  fat  carbon 
into  sugar  would  entail  a  minimum  loss  of  energy  available  for 
mechanical  work  of  29  per  cent. 

Atwater  and  Benedict^  claim  to  have  confirmed  these  results, 
although  unfortunately  the  diets  provided  were  not  strictly  fat- 
proteid  and  carbohydrate-proteid,  but  were  really  mixed  diets. 

Thus  J.  W.  C,  during  two  periods  of  twenty- two  days  each, 
ingested  each  day  diets  which  produced  the  following  metabo- 
lism as  calculated  from  the  body's  excreta: 

Calculated  Metabolism. 

Period  I.  Period  II. 

Carbohydrate  Diet.  Fat  Diet. 

Proteid 434  calories.  489  calories. 

Fat 1288         "  3190         " 

Carbohydrates 3371         "  1465         " 

Total  metabolism 5093  5144 

The  average  of  work  accompHshed  and  body  heat  evolved 
each  day,  as  measured  in  the  Atwater  calorimeter,  were  as 
follows : 

Work  and  Metabolism  as  Directly  Measured. 

Carbohydrate  Diet.     Fat  Diet. 

Mechanical  work 543  calories.  550  calories. 

Body  heat 4593         "  4555 

Total  metaboHsm 5136  5105 

The  work  was  done  on  a  stationary  bicycle.  It  is  evident  that 
the  work  could  not  have  been  at  the  expense  of  proteid  metabo- 
lism. But  it  is  also  plain  that  the  work  could  have  been  derived 
from  carbohydrate  combustion  even  on  the  "fat"  diet  of  Period 
11. 

These  experiments,  however,  were  the  first  to  demonstrate 
exactly  that  mechanical  work  was  done  at  the  expense  of  a 
dynamic  equivalent  of  metabolism, — a  splendid  confirmation  of 
the  law  of  the  conservation  of  energy. 

In  one  other  experiment  Atwater  and  Benedict  calculated  for 
J.  W.  C.  a  metabolism  amounting  to  9981  calories,  divided  as 
follows:     Proteid,    478   calories;   fat,  7744  calories;    carbohy- 

'  Atwater  and  Benedict:  "Experiments  on  the  Metabolism  of  Matter  and 
Energy  in  the  Human  Body,"  1903,  U.  S.  Dept.  of  Agriculture,  Bulletin  136. 


INFLUENCE   OF   MECHANICAL   WORK   ON   METABOLISM.     169 

drates,  1759.  The  man  worked  for  sixteen  hours  on  the 
bicycle.  The  work  done  measured  an  equivalent  of  1482 
calories;  the  body  heat  production  was  7382  calories,  both  of 
which  were  measured  in  the  Atwater  calorimeter,  and  the  total 
energy  loss  reached  9314  calories,^  a  height  of  metabolism 
attained  also  by  Maine  lumbermen^  actively  employed  (p.  187). 

Although  from  Zuntz's  work  it  seems  proved  that,  in  fur- 
nishing power  for  mechanical  work,  carbohydrates  and  fat  are 
replaceable  one  for  the  other  according  to  their  dynamic  values, 
there  is  a  well-founded  belief  that  work  may  be  obtained  in 
larger  quantity  from  an  individual  if  carbohydrates  be  available. 

Schumburg^  finds  that  ingestion  of  carbohydrates  enables 
a  fatigued  muscle  to  contract  more  powerfully.  Hellesen* 
states  that  in  doing  mechanical  work  in  the  morning  before 
breakfast,  an  improved  capacity  occurs  thirty  to  forty  minutes 
after  ingesting  sugaro 

The  ready  exhaustion  of  diabetics  who  cannot  bum  dextrose 
confirms  this  observation. 

Lee  and  Harrold^  have  found  evidences  of  great  fatigue  in 
the  excised  muscles  of  a  cat  from  which  the  readily  combustible 
sugar  had  been  removed  by  rendering  the  cat  diabetic  with 
phlorhizin.  A  cat  treated  similarly,  but  whose  organism  had 
been  flooded  with  sugar  by  ingestion  before  killing  the  animal, 
showed  a  much  larger  capacity  for  muscular  contraction. 

The  writer®  while  injecting  phloretin  solutions  into  the 
jugular  vein  of  fasting  rabbits,  diabetic  through  phlorhizin, 
noticed  that  seven  out  of  eight  rabbits  had  convulsions,  while 
normal  rabbits  were  not  so  affected.  Four  died  and  three  lost 
motor  control  of  the  muscles  of  their  limbs.     In  these  three 


^  The  calories  calculated  from  the  metabolism  and  those  directly  measured 
by  the  calorimeter  did  not  exactly  agree  in  this  particular  instance — an  exception 
in  a  brilliant  series. 

^  Woods  and  Mansfield:  U.  S.  Dept.  of  Agriculture,  1904,  Bulletin  149. 

^  Schumburg:  "Archiv  fiir  Physiologie,"  1896,  p.  537. 

*  Hellesen:  "Skan.  Archiv  fiir  Physiologie,"  1904,  Bd.  xvi,  p.  139. 

'Lee  and  Harrold:  Proceedings  of  the  American  Physiological  Society, 
"American  Journal  of  Physiology,"  1900,  vol.  iv,  p.  ix. 

"  Lusk:  "Zeitschrift  fiir  Biologic,"  1898,  Bd.  xxxvi,  p.  109. 


lyo  SCIENCE   OF   NUTRITION. 

there  was  an  increased  dextrose  elimination  in  the  urine  on 
account  of  the  passage  of  the  glycogen  content  of  the  organs 
into  the  blood,  which  glycogen  would  normally  be  immediately 
available  for  muscular  activity  (p.  71).  The  animals  which 
survived  the  convulsions  obtained  control  of  their  muscles 
in  two  to  four  hours.  This  indicates  a  slow  preparation  from 
fat  of  materials  available  for  the  production  of  muscle  work. 

Schumburg^  finds  that  coffee  and  tea  have  no  recuperative 
power  over  the  muscles  of  a  fatigued  organism,  except  when 
taken  with  other  foods,  and  that  the  stimulating  action  of  al- 
cohol is  only  temporary.  Hellesen,^  exercising  before  breakfast, 
finds  that  the  effect  of  taking  tea  is  almost  negligible,  and  that 
the  effect  of  alcohol  is  at  first  to  increase  the  muscle  power  but 
that  after  twelve  to  forty  minutes  there  is  a  decrease  in  power 
which  lasts  for  two  hours.  No  such  depression  occurs  after 
taking  sugar.  It  is  obvious  that  alcohol  is  not  beneficial  when 
muscular  work  is  to  be  accomplished. 

The  carbon  dioxid  produced  as  a  result  of  mechanical  work 
is  quickly  eliminated  through  the  lungs.  Higby  and  Bowen' 
find  that  the  increased  elimination  begins  twenty  seconds  after 
the  commencement  of  bicycle  riding  and  reaches  its  maximum 
in  about  two  minutes.  At  this  point  it  remains  constant  from 
minute  to  minute  provided  the  same  amount  of  work  is  done. 
This  principle  has  been  frequently  demonstrated  by  Zuntz  and 
his  pupils.  It  is  evident,  however,  that  the  quantity  of  carbon 
dioxid  excretion  for  the  unit  of  work  accomplished  will  be  less 
during  starvation  and  on  a  fat  diet  than  when  carbohydrates 
are  ingested,  by  reason  of  the  higher  heat  value  of  fat 
carbon.* 

It  has  already  been  shown  that  25  per  cent,  of  the  total  energy 
of  the  increase  above  the  resting  metabolism  as  caused  by  work 
is  converted  into  mechanical  energy  by  a  person  turning  the 
wheel  of  an  ergostat  with  his  arms. 

'  Schumburg:  Loc.  cit.  ^  Hellesen:  Loc.  cit. 

'  Higby  and  Bowen:  "American  Journal  of  Physiolog)-,"  1904,  vol.  xii,  p.  335. 
*  Johansson  and  Koraen:  "Skand.  Archiv  fiir  Physiologic,"   1902,  Bd.  xiii, 
p.  251. 


INFLUENCE   OF   MECHANICAL   WORK   ON   METABOLISM.     171 

Katzen stein  ^  has  shown  a  still  more  economical  utilization  of 
the  fuel  when  the  work  accomphshed  is  climbing,  about  35  per 
cent,  of  the  total  increase  in  metabolism  being  then  converted 
into  mechanical  effect.  Walking,  the  commonest  muscular  ex- 
ercise, is  accomplished  with  the  greatest  economical  efficiency. 

A  great  many  interesting  details  have  been  worked  out  in 
Zuntz's  laboratory  by  his  pupils.  The  following  epitome  of 
long  investigations  shows  the  comparative  energy  equivalents 
necessary  for  a  dog,  horse,  and  man  to  move  one  kilogram  of 
body  weight  one  meter  with  a  given  rapidity  along  a  horizontal 
plane  or  to  lift  one  kilogram  of  body  weight  one  meter  high.^ 
The  experiments  were  made  by  placing  the  individual  on  a 
moving  platform,  the  speed  and  incline  of  which  could  be  varied. 

ENERGY   REQUIREMENTS    OF   DIFFERENT   ANIMALS    IN   PER- 
FORMANCE   OF   THE    SAME   AMOUNT   OF 
MECHANICAL  WORK. 


Animal. 


Dog... 
Dog... 
Horse. 
Man.. 


F. 
Normal  locomotion. 

F. 
Slow  locomotion ... 

R. 
Normal 

R. 
Slow 


Weight. 


26.9 

26.9 

456.8 

55-5 
72.9 
67.9 
80.0 
88.2 
72.6 
81. 1 
80.0 

86.5 

86.5 

68.5 

68.5 


Energy  Requirement  in 

KiLOGRAMMETERS . 


For  moving 

horizontally 

I     Kg.     I 

Meter. 


0-495 
0.501 
0.137 

0-334 
0.217 
0.211 
0.288 
0.263 
0.284 
0.231 
0.244 

0.219 
0-233 


For  raising  i 

Kg.    I    Meter 

high. 


1 


2-954 
3-259 
2.912 

2-857 
3.190 
3.140 

3-563 
3-555 
2.913 
2.912 
2.729 


I-      2.746 


2.846 


Velocity  in 
Meters 

PER  MlN- 
u  t  E  OF 
HORIZONTAL 
MOVEMENT. 


78-57 

78-57 
74.48 
71.32 
71.46 

51-23 
42.34 
62.04 
60.90 
56-54 

66.94 

35-92 

63-95 

34-58 


Incline  of 
ROAD  IN  per 
cent.  during 
Climbing  Ex- 
periment. 


17.2 
10.3 

9-6-13-3 

6-5 

30.7-62 
23-30-5 


}■     23.3 


^  Katzenstein:  "Pfltiger's  Archiv,"  1891,  Bd.  .xlix,  p.  379. 
^  Frentzel  and  Reach:  Ibid.,  1901,  Bd.  Ixxxiii,  p.  494. 


172  SCIENCE    OF    NUTRITION. 

A  study  of  the  foregoing  table  will  show  that  it  requires  much 
less  energy  for  a  horse  to  move  one  kilogram  of  his  weight  one 
meter  horizontally  than  for  a  dog  to  do  the  same  at  the  same 
velocity.  It  also  appears  that  a  man  of  small  weight  requires 
more  energy  to  a  unit  of  substance  than  a  man  of  large  size. 
This  rule  has  been  confirmed  in  dogs  by  Slowtzoff/  who  shows 
that  energy  amounting  to  0.529  kilogrammeter  is  required  for 
one  meter  horizontal  motion  by  a  dog  weighing  37  kilograms 
and  1. 1 38  kilogrammeters  by  a  dog  weighing  5.5  kilograms. 
Slowtzoff  does  not  find  that  this  variation  is  proportional  to  the 
skin  area  of  the  animal. 

The  table  also  shows  that  there  is  little  variation  in  the  dog, 
horse  and  man  in  the  amount  of  energy  necessary  to  raise  one 
kilogram  of  body  substance  one  meter  high. 

It  is  possible  to  calculate  the  food  ration  for  a  march  if  the 
figures  given  in  the  table  be  employed.  If  it  be  assumed  that 
a  man  weighing  70  kilograms  travels  74.4  meters  a  minute  he 
will  accompUsh  4.46  kilometers  or  2.7  miles  per  hour.  If  it 
requires  the  energy  equivalent  of  0.217  kilogrammeters  to  move 
one  kilogram  of  his  weight  one  meter  it  will  require  67,747  kilo- 
grammeters (0.217  X  70  X  4460)  to  move  him  4.46  kilometers, — 
67,747  kilogrammeters  being  equivalent  to  159,205  calories. 
This  is  the  equivalent  of  17.1  grams  of  fat  which  may  be  added 
to  the  maintenance  resting  dietary  requirement  to  supply  the 
energy  necessary  for  an  hour's  quiet  walk  on  a  level  road.  If 
the  road  be  inclined  so  that  the  man  raises  himself  500  meters 
during  the  hour's  walk,  the  metabolism  will  be  still  further  in- 
creased. The  work  of  ascent  will  be  his  weight  multiplied  by 
the  height  of  his  climb,  or  35,000  kilogrammeters.  The  expen- 
diture of  energy  by  the  body  in  order  to  accomplish  this  work  is 
threefold  the  work  done,  or  105,000  kilogrammeters,  which  equals 
246.750  calories,  or  26.5  grams  of  fat.  The  hour's  walk  in 
this  case  would  require  the  production  of  an  energy  equivalent, 
above  the  resulting  metabolism,  amounting  to  that  contained  in 
43.6  grams  of  fat, — that  is,  17.1  grams  for  a  forward  locomotion 

'  Slowtzoff:  "Pfluger's  Archiv,"  1903,  Bd.  xcv,  p.  190. 


INFLUENCE    OF   MECHANICAL   WORK    ON   METABOLISM.     1 73 

of  4.46  kilometers  and  26.5  grams  to  lift  the  body  to  an  altitude 
of  500  meters. 

In  the  last-mentioned  table  it  is  seen  that  there  is  an  increase 
in  the  metabolism  for  a  unit  of  horizontal  motion  when  the 
progress  of  the  individual  is  very  slow.  This  is  explained  by 
the  fact  that  speed  of  progress  was  half  the  normal,  was  unusual, 
and  forced. 

The  mle  is  that  the  metabolism  increases  with  speed  in  men 
(0.39  to  0.84  per  cent,  per  meter  increase  between  60  and  100 
meters  per  minute)  and  in  horses  (1.03  per  cent,  per  meter  in- 
crease above  78  meters  per  minute),  but  this  is  not  seen  in  dogs.^ 

Katzenstein'  finds  that  the  metabohsm  during  the  descent 
of  a  mountian  is  less  by  10  per  cent,  than  the  increase  caused  by 
walking  on  a  level  surface.  The  muscles  which  act  to  inhibit  a 
too  rapid  descent  are  not  required  to  be  so  active  as  those  which 
give  forward  impetus  to  the  body  on  a  level  road. 

This  idea  has  recently  been  still  further  investigated  by 
mountaineers^  who  compared  the  actual  heat  production  with 
the  energy  of  metabolism  during  one  minute,  for  horizontal 
motion,  and  for  ascent  and  descent  of  a  mountain  path  which 
had  a  25  per  cent.  incHne.     The  results  were  as  follows: 

Ascent  28.8  Horizontal        Descent 

Meters.  100  Meters.      76  Meters. 

Calories  of  energ}' of  metabolism ....69.3  67.8  40.8 

Calories  of  heat  liberated 46.9  67.8  85.5 

The  smallest  liberation  of  heat  occurred  during  the  ascent 
of  the  mountain  at  the  time  when  the  energy  of  metabolism  was 
being  converted  into  energy  of  position. 

The  largest  heat  production  occurred  during  the  descent  of 
the  mountain.  The  metabolism  was  the  least,  but  energy  of 
position  was  converted  into  heat  through  the  vibration  of  the 
body  at  each  footfall. 

^  Zuntz:  "Pfliiger's  Archiv,"  1903,  Bd.  xcv,  p.  192. 
^  Katzenstein:  Loc.  cit.,  p.  376. 

^  Zuntz,  Loewi,  Miiller,  and  Caspari:  "Hohenklima  und  Bergwanderungen 
in  ihrer  Wirkung  auf  den  Menschen,"  1906. 


174  SCIENCE    OF   NUTRITION. 

Zuntz  and  Schumburg '  show  that  a  well-placed  knapsack 
is  carried  by  a  soldier  with  very  little  increased  expenditure  of 
energy.  A  soldier  weighing  74.45  kilograms,  moving  at  the  rate 
of  74.4  meters  per  minute,  requires  541.8  calories  for  the  move- 
ment of  one  kilogram  of  substance  1000  meters.  The  same 
soldier,  laden  with  a  knapsack  weighing  19  kilograms  (total 
weight=  93.45  kilograms),  requires  only  502.3  calories  to  move 
one  kilogram  1000  meters.  A  pack  may  therefore  be  more 
economically  moved  than  the  body's  substance,  which  is  an 
argument  against  obesity. 

If  the  knapsack  be  badly  placed,  or  if  the  body  be  sore  and 
weary,  Zuntz  and  Schumburg  find  an  increase  in  the  metabo- 
lism of  a  marching  soldier. 

Lavonius^  finds  the  maximum  amount  of  work  attainable 
from  a  trained  wrestler  of  great  reputation  to  be  the  equivalent 
of  30  kilogrammeters  per  second. 

A  subject  of  very  great  interest  is  the  result  of  training.  It 
is  well  known  that  if  a  cobbler,  for  example,  be  removed  from 
his  trade  and  be  compelled  to  climb  a  mountain,  he  will  at  first 
be  of  little  use  as  compared  with  a  Swiss  guide.  But  after  con- 
stant practice  the  blood-vessels  open  at  once  in  response  to  the 
needs  of  the  muscles  and  the  heart  expends  less  energy;  un- 
necessary motions  with  the  arms  and  legs  are  diminished  in 
number;  the  strain  for  the  accompHshment  of  a  given  piece  of 
work  diminishes;  the  thorax  enlarges  to  promote  readier  respira- 
tion; the  man  becomes  "trained,"  and  there  may  be  a  les- 
sened metabolism  for  the  fulfillment  of  a  definite  amount  of  work. 

The  experimental  measurements  of  the  efficacy  of  the 
working  organism  as  described  above  were  made  on  well-trained 
men,  a  difference  on  account  of  training  having  been  early 
recognized  by  Zuntz. 

Certain  differences  between  the  urine  of  trained  and  untrained 
men  have  already  been  noted  (p.  63). 

'Zuntz  and  Schumburg:  "Studien  zu  einer  Physiologic  des  Marsches," 
Berlin,  1901. 

'  Lavonius:  "Skan.  Archiv  fiir  Physiologie,"  1905,  Bd.  xvii,  p.  196. 


INFLUENCE    OF    MECHANICAL    WORK    ON    METABOLISM.     1 75 

Biirgi^  made  some  investigations  upon  an  individual  before 
and  after  training  for  mountain  climbing.  The  ascents  were 
made  at  different  altitudes  on  the  roadbed  of  mountain  railways, 
and  the  carbon  dioxid  elimination  was  measured.  The  results 
are  shown  in  the  following  table: 

EFFECT  OF  "TRAINING"  ON  METABOLISM. 


Place. 

-Altitude  in 
Meters. 

Incline  of 

R0.4D  IN  PER 
CENT. 

CO2   Excretion   per   Kgm.   of 
Work. 

Untrained. 

Trained. 

Brienz 

Gornergrat 

Brienz 

Gornergrat 

620 

2987 

690 

3021 

17.29 

19-3  . 
19.0 

19-3 

2.430 
2. 711 
2.251 

2.445 

2.103 
2.268 
2.063 
2. 117 

It  is  evident  from  this  that  a  trained  mountaineer  accom- 
plishes his  work  at  the  expense  of  less  metabolism  than  when 
untrained.  Also  that  at  a  moderately  high  altitude  (3000 
meters=  522  mm.  of.  mercury,  barometric  pressure)  the  trained 
organism  is  as  efficient  for  mechanical  work  as  at  the  sea  level; 
whereas  the  untrained  man  requires  a  much  greater  metaboHsm 
to  accomplish  a  unit  of  work  at  the  higher  altitude  than  at  the 
lower. 

At  still  higher  altitudes  there  is  always  an  increase  in  the 
amount  of  metabolism  necessary  to  accomphsh  mechanical 
effort,  and  this  will  be  discussed  in  another  chapter. 

Another  fact  of  importance  is  that  the  effect  of  training 
especially  affects  the  muscles  involved  in  the  particular  move- 
ment, and  not  those  which  do  not  contract.  Thus  Zuntz^  found 
that  a  dog  trained  for  horizontal  motion  on  a  level  street  required 
II 79  small  calories  to  move  one  kilogram  body  weight  looo 
meters  and  7.668  small  calories  to  raise  one  kilogram  body  weight 
one  meter  high.  The  dog  was  then  gradually  trained  to  ascend 
an  incline.    After  two  years  he  required  only  5.868  small  calories 

'Biirgi:  "Archiv  fiir  Physiologie,"  1900,  p.  509. 
-  Zuntz:  "Pfliiger's  Archiv,"  1903,  Bd.  xcv,  p.  200. 


176  SCIENCE   OF   NUTRITION. 

to  lift  one  kilogram  one  meter,  but  he  required  1343  small  cal- 
ories per  kilogram  for  horizontal  locomotion  through  1000  meters. 
Therefore  the  specifically  trained  muscles  work  more  economi- 
cally than  those  which  are  at  the  time  but  little  used. 

A  man  trained  for  mountaineering  will  often  find  himself 
uncomfortable  when  walking  on  a  level  road.  The  mountaineer 
will  not  find  the  bicycle  an  easy  means  of  locomotion/  nor  will 
the  bicycHst  unscathed  essay  the  mountain. 

A  benefit  derived  from  riding  a  horse  is  the  shaking  of  the 
internal  organs,  which  is  also  achieved  by  descending  a  steep 
pathway.  This  may  be  beneficial  to  the  life  processes  in  such 
a  comparatively  immobile  organ  as  the  liver  for  example.  It 
also  appears  to  promote  a  freer  evacuation  of  the  bowels. 

In  swimming  there  is  considerable  respiration  gymnastics.^ 
The  water  pressure  upon  the  thorax  is  the  equivalent  of  the 
weight  of  an  8-kilogram  sand-bag,  which  the  swimmer  seeks  to 
counterbalance  by  increasing  the  pressure  in  his  lungs  through 
puffing  with  his  lips.  By  turning  over  on  the  back  the  swimmer 
removes  this  respiratory  influence.  Cold  water  stimulates 
metabolism  (p.  93),  but  the  effect  of  the  salt  in  ordinary  sea 
water  is  certainly  negligible. 

There  can  be  little  doubt  that  exercise,  especially  in  the  open 
air,  strengthens  the  organism  and  therefore  tends  to  prolong  life. 
Sometimes  muscular  exercise  is  mistakenly  considered  as  favor- 
ing intellectual  activity.  Yet  college  presidents  are  not  selected 
from  the  ranks  of  prize-fighters. 

^  Concerning  work  expended  in  bicycle  riding  see  Berg,  Du  Bois-Reymond 
and  L.  Zuntz:  "Archiv  fiir  Physiologie,"  Supplement,  1904,  p.  20. 
^  R.  du  Bois-Reymond,  Ibid.,  1905,  p.  253. 


CHAPTER  IX. 
A  NORMAL  DIET. 

The  principles  of  metabolism  have  been  sufficiently  ex- 
plained in  the  foregoing  chapters  to  make  it  possible  to  under- 
stand the  basis  of  a  diet  which  shall  be  physiologically  rational. 

It  has  been  seen  that  the  average  starvation  metaboHsm  of  a 
vigorous  man  at  light  work  and  weighing  70  kilograms  approxi- 
mates 2240  calories,  or  32  calories  per  kilogram.  It  is  obvious 
that  this  quantity  of  energy  must  be  contained  in  the  daily  food, 
and  a  httle  more  to  counterbalance  the  "specific  dynamic"  or 
heat-increasing  power  of  the  foodstuffs,  if  the  individual  is  to  be 
maintained  in  calorific  equihbrium.  It  has  been  seen  that 
when  an  average  mixed  diet  is  ingested  the  maintenance  require- 
ment is  between  ii.i  and  14.4  per  cent,  above  the  starvation 
minimum  (p.  139).  This  would  amouQt  to  from  2488  to  2562 
calories,  or  from  35.5  to  36.6  calories  per  kilogram  of  body 
weight  in  the  case  of  the  individual  just  referred  to. 

Since  man  through  clothing  shuts  himself  off  from  the  reflex 
action  of  cold  on  the  skin,  the  greatest  factor  which  tends  to 
increase  his  metabolism  is  mechanical  work,  and  the  total  calories 
required  are  here  dependent  on  the  kind  and  the  amount  of  the 
work  accomphshed.  The  requirements  in  this  regard  have 
already  been  discussed. 

A  point  of  great  interest  is  that  of  the  proper  proportion  in 
which  the  individual  foodstuffs  should  be  put  together  in 
making  up  a  ration. 

Voit  defines  a  food  as  a  well-tasting  mixture  of  foodstuffs  in 
proper  quantity  and  in  such  a  proportion  as  will  least  burden 
the  organism.     What  is  the  proper  proportion  ? 

Voit^  gives  the  following  ration  for  the  use  of  an  average 

^  Voit:  "Physiologic  des  Stoffwechsels,"  1881,  p.  519. 
12  177 


lyS  SCIENCE    OF   NUTRITION. 

laborer,  such  as  a  soldier  in  a  garrison, — that  is,  for  a  man  at 
work  from  eight  to  ten  hours  a  day:  Proteid,  ii8  grams;  car- 
bohydrates, 500  grams;  fat,  56  grams.  This  diet  contains 
3055  calories. 

The  allowance  of  118  grams  of  proteid  has  provoked  much 
discussion.  The  original  figures  were  obtained  by  Voit  by  aver- 
aging the  proteid  metabolism  of  many  laboring  men.  This 
requirement  of  proteid  was  therefore  obtained  by  the  statistical 
method,  which  simply  showed  what  the  average  laborer  in  habit 
destroyed.  For  the  same  class  of  artisan,  the  diet  given  by 
Rubner  calls  for  127  grams  of  proteid;  by  Atwater  125  grams; 
and  Lichtenfelt '  confirms  Voit's  average  as  being  the  quantity 
of  proteid  taken  by  laborers  in  northern  Italy. 

For  men  at  hard  labor,  such  as  soldiers  in  the  field,  even 
higher  quantities  of  proteid  are  commended, — by  Voit,  145 
grams;  by  Rubner,  165  grams;  by  Atwater,  150  grams.  These 
figures  again  are  based  on  statistics.  Quite  recently  Woods  and 
Mansfield^  found  that  the  average  proteid  in  the  ration  of  fifty 
lumbermen  is  164.1  grams. 

In  striking  contrast  to  this  Siven^  at  the  age  of  thirty-one 
and  a  half  years  and  weighing  65  kilograms,  finds  he  can  main- 
tain himself  in  nitrogen  equihbrium  for  a  short  period  on  a  diet 
containing  between  4  and  5  grams  of  nitrogen,  or  25  to  31  grams 
of  proteid.  In  fact,  in  one  experiment  the  food  contained  4 
grams  of  nitrogen,  of  which  2.4  grams  only  were  in  15.4  grams 
of  true  proteid  and  the  balance  in  amino  acids  and  other  nitro- 
genous non-proteid  matter  of  vegetable  origin.  Here  nitrogen 
equilibrium  was  nearly  attained,  the  nitrogen  ingested  being  4, 
and  that  excreted  4.28  grams.  The  food  given,  which  was  rich 
in  carbohydrates,  contained  2717  calories,  or  43  calories  per  kilo- 
gram, and  the  total  metabolism  as  estimated  by  respiration  ex- 
periments indicated  a  heat  production  of  2082  or  32  calories  per 


'  Lichtenfelt:  "Pfliiger's  Archiv,"  1903,  Bd.  xcix,  p.  i. 

'Woods  and   Mansfield:   "Studies  of  the  Food  of  Maine  Lumbermen," 
U.  S.  Department  of  Agriculture,  1904,  Bulletin  149. 

^Siven:  " Skan.  Archiv  fiir  Physiologic,"'  1901,  Bd.  xi,  p.  308, 


A  NORMAL   DIET.  1 79 

kilogram.  Here  was  practically  nitrogen  equilibrium  main- 
tained at  the  minimum  level,  and  a  low  total  metabolism  which 
was  largely  at  the  expense  of  carbohydrates. 

It  will  be  recalled  that  the  quantity  of  nitrogen  in  the  urine 
in  the  average  fasting  man  who  has  been  previously  well  nour- 
ished, is  ID  grams,  a  minimum  which  is  only  reducible  by  carbo- 
hydrate ingestion. 

The  experiments  of  Siven  did  not  satisfy  people  that  a  low 
proteid  metabolism  was  compatible  with  continued  health  and 
strength.  Munk^  and  Rosenheim^  both  found  that  dogs  given 
a  quantity  of  proteid  sufficient  only  to  maintain  nitrogen  equilib- 
rium gradually  lost  strength  and  became  afflicted  with  diges- 
tive disturbances.  These  experiments  fortified  the  idea  of  the 
benefits  to  be  derived  from  a  diet  containing  more  proteid  than 
was  necessary  for  the  maintenance  of  nitrogen  equilibrium — 
a  luxus  consumption.  Rubner  declares  that  a  large  proteid 
allowance  is  the  right  of  civilized  man. 

The  tradition  that  a  continued  liberal  allowance  of  proteid 
in  a  diet  is  a  prerequisite  for  the  maintenance  of  bodily  vigor 
has  been  dispelled  by  Chittenden^  and  his  co-workers,  of  whom 
Mendel  is  the  most  prominent. 

Professor  Chittenden  had  suffered  from  persistent  rheuma- 
tism of  the  knee-joint  and  determined  on  a  course  of  dieting 
which  should  largely  reduce  the  proteid  and  the  calorific  intake. 
The  rheumatic  trouble  disappeared,  and  minor  troubles  such 
as  "sick  headaches,"  and  bihous  attacks  no  longer  recurred 
periodically  as  before.  "There  was  a  greater  appreciation  of 
such  food  as  was  eaten;  a  keener  appetite  and  more  acute  taste 
seemed  to  be  developed,  with  a  more  thorough  liking  for  simple 
foods."  During  the  first  eight  months  of  the  dieting  there  was 
a  loss  of  eight  kilograms  of  body  weight.  Thereafter  for  nine 
months  the  body  weight  remained  stationary.  "Two  months  of 
the  time  were  spent  at  an  inland  fishing  resort,  and  during  a 

^  Munk:  "Archivfiir  Phvsiologie,"  1S91,  p.  338. 

^  Rosenheim:  Ibid.    p.  341. 

^  Chittenden:  "  Physiological  Economy  in  Nutrition,"  1904. 


l8o  SCIENCE    OF    NUTRITION. 

part  of  this  time  a  guide  was  dispensed  with  and  the  boat  rowed 
by  the  writer  frequently  six  to  ten  miles  in  a  forenoon,  some- 
times against  head  winds  (without  breakfast)  and  with  much 
greater  freedom  from  fatigue  and  muscular  soreness  than  in 
previous  years  on  a  fuller  dietary." 

During  the  period  of  nine  months  the  nitrogen  of  the  urine 
was  determined  daily.  The  average  was  5.69  grams.  During 
the  last  two  months  and  a  half,  the  average  eUmination  was  5.40 
grams  for  a  body  weight  of  57.5  kilograms.  Experiments 
showed  that  about  one  gram  of  nitrogen  was  eliminated  in  the 
feces  and  that  nitrogen  equilibrium  could  be  maintained  with 
dietaries  of  low  calorific  values  (1613  and  1549  calories=28  and 
27  calories  per  kilogram)  containing  6.40  and  5.86  grams  of 
nitrogen.  These  figures  correspond  to  diets  containing  40.0  to 
36.6  grams  of  proteid  instead  of  the  118  grams  honored  by  habit 
and  tradition.  Professor  Chittenden  proclaims  such  a  diet  as  of 
the  highest  importance  to  health. 

The  case  of  Chittenden  recalls  a  note  from  an  early  convert 
to  the  "Graham  system"  of  vegetarianism.  Sylvester  Graham, 
in  1829,  began  the  advocacy  of  moderation  in  the  use  of  a  diet 
consisting  of  vegetables,  Graham  bread  (made  of  unbolted  flour), 
fruits,  nuts,  salt  and  pure  water,  and  excluding  meat,  sauces, 
salads,  tea,  coff"ee,  alcohol,  pepper,  and  mustard.  The  letter 
reads  as  follows:^  "The  first  three  months  of  my  experiment 
on  the  Graham  system  was  attended  by  a  loss  of  20  to  30  pounds 
of  flesh.  Some  of  my  neighbors  expostulated  with  me,— told 
me  I  should  destroy  myself  by  starvation,  and  it  was  even  re- 
ported in  a  neighboring  town  that  I  had  actually  died  from  that 
cause.  But  my  appetite  was  increasingly  good  and  my  health 
was  increasing,  and  in  a  short  time  my  headaches,  colds,  cos- 
tiveness,  and  rheumatism  left  me  entirely,  together  with  my 
hypochondriacal  and  gloomy  state  of  mind,  and  have  not  re- 
turned since,  notwithstanding  I  have  been  as  much  exposed 
to  wet  and  cold  as  at  any  period  of  my  life." 

'  Charles  Clapp:  "The  Graham  Journal  of  Health  and  Longevity,"  Boston, 
1837,  vol.  i,  p.  57. 


A   NORMAL    DIET. 


i8i 


Chittenden's  experiments  were  not  confined  to  an  indi- 
vidual nor  to  a  single  group  of  individuals.  Other  experi- 
ments were  made  on  professional  men,  on  student  athletes  in 
training,  and  on  soldiers  under  mihtary  regime.  The  daily 
nitrogen  in  the  urine  in  periods  extending  from  five  to  nine 
months  averaged  as  follows  in  the  individuals  belonging  to 
the  three  groups: 


Professors  and  Teachers. 

University  Athletes. 

United  States  Soldiers. 

Weight  in  Kg. 

N    IN 

Urine  inG. 

Weight  in  Kg. 

N    IN 

Urine  inG. 

Weight  in  Kg. 

N.  IN 

Urine  inG. 

S7-0 

70.0 

65.0 ,  - 

65-0 

61.5 

5-69 
6.53 
7-43 
8.99 
8.58 

71.0 

61  0             .    . 

1 

9-37     i 
10.41 

8.88 

9.04 

7-47 

7-58 
10.09 
11.06 

62 

7.42 

7-03 
7.26 
8.17 
8.39 
7-13 
8.91 
7.84 
8.05 
7.38 
8.25 
8.08 
8.61 

Co 

78.0 

183.0 

!  62.0 

56-0 

73-0 

71:. 0 

,60 

■58 

60 

i  r, 

71 

72 

62 

59 

55 

65 

Cf 

At  convenient  periods  during  the  above  experiments  it  was 
determined  that  the  body  was  being  maintained  in  nitrogenous 
equilibrium  on  the  diet  which  gave  rise  to  the  above  amounts 
of  urinary  nitrogen  (p.  157). 

The  professional  group  alleged  a  greater  keenness  for  its 
work,  the  athletic  group  won  championships  in  games,  and  the 
soldiers  maintained  perfect  health  and  strength,  many  professing 
repugnance  to  meat  when  they  were  allowed  it  after  five  months 
of  practical  abstinence. 

Although  it  is  possible  that  the  alleged  improved  mental  con- 
dition^ may  have  been  due  to  mental  suggestion  (p.  243),  still 
the  fact  remains  that  it  has  been  proved  by  Chittenden's  work 
that  the  allowance  of  proteid  necessary  for  continued  health  and 

^  Chittenden:  Loc.  cit.,  p.  51. 


l82  SCIENCE   OF   NUTRITION. 

strength  may  be  reduced  during  many  months  to  half  or  less  of 
what  the  habit  of  the  appetite  suggests. 

It  remains  to  be  seen  whether  this  quantity  of  proteid  in 
the  ration,  which  is  not  greater  than  the  body  would  metabohze 
in  starvation,  is  advisable  as  a  program  for  the  whole  of  one's 
adult  life. 

The  foods  with  the  strongest  flavors  are  meats,  which  there- 
fore add  relish  to  a  repast,  and  stimulate  the  digestive  secretions. 

Chittenden  beHeves  that  the  large  quantity  of  proteid  in  an 
ordinary  diet  is  due  to  self-indulgence.  He  protests  against  such 
indulgence,  and  thinks  that  a  needless  strain  is  thereby  imposed 
upon  the  liver,  kidneys,  and  other  organs  concerned  in  the  trans- 
formation and  elimination  of  the  end-products  of  proteid 
metabolism, 

Lichtenfelt,^  on  the  other  hand,  shows  that  while  there  is  no 
statistical  difference  in  the  height  of  individuals  as  due  to  oc- 
cupation, still  the  people  of  Southern  Italy  are  not  so  large  nor 
so  well  developed  physically  as  their  fellows  of  Northern  Italy. 
He  explains  this  stunted  growth  as  due  to  a  low  proteid  and  cal- 
orific intake  in  the  food. 

Hirschfeld  ^  finds  that  the  actual  ration  of  a  German  soldier 
contains  98  grams  of  proteid,  with  no  untoward  results.  He 
states  that  writers  on  economics,  who  believe  the  German  popu- 
lace underfed  because  they  do  not  have  118  grams  of  proteid 
daily,  are  unduly  pessimistic. 

Although,  as  has  been  stated,  the  battle-ground  has  been 
over  the  allowance  of  118  grams  in  Voit's  dietary,  it  will  be  sur- 
prising to  many  to  learn  that  Voit  himself  has  said  little  on  the 
subject.  He^  has  shown  that  a  vegetarian  can  live  in  nitro- 
genous equilibrium  on  a  diet  containing  48.5  grams  of  proteid 
and  that  an  active  working  man  weighing  74  kilos  may  get  along 
on  less  than  118  grams.  He  discourages  the  tendency  to  eat 
meat  in  excess.     He  also  discourages  the  practice  of  vegetarians 

'  Lichtenfelt:  "Pfluger's  Archiv,"  1905,  Bd.  cvii,  p.  57. 
'Hirschfeld:  "Archiv  fiir  Physiologic,"  1900,  p.  380. 
'Voit:  "Zeitschrift  fiir  Biologic,"  1889,  Bd.  xxv,  p.  278. 


A   NORMAL   DIET.  1 83 

who  overload  the  digestive  tract  with  the  coarser  kinds  of  vege- 
table foods  which  leave  large  indigestible  residues. 

It  is  not  to  be  denied  that  50  grams  of  proteid  (containing 
8  grams  of  nitrogen)  are  apparently  able  to  maintain  the  adult 
body  machine  in  perfect  repair.  Vegetarians,  fruitarians  ^  (who 
hve  on  fruit  and  nuts)  and  vigorous  adults  who  largely  exclude 
proteid  from  the  diet,  are  evidently  able  to  live  in  health  and 
strength  upon  this  quantity.  It  must  be,  however,  that  more 
than  this  amount  is  advisable  during  growth  or  convalescence 
from  wasting  disease,  or  during  the  muscular  hypertrophy 
which  accompanies  preliminary  training  for  athletic  effort. 

Abderhalden^  mentions  the  fact  that  whereas  various  body 
tissues  are  constructed  of  different  proteids,  so  a  large  variety 
of  amino  acids  must  be  available  for  their  proper  replenishment. 
Hence,  it  is  reasonable  to  assume  that  a  considerable  excess 
of  food  proteid  is  essential  to  supply  the  special  amino  products 
for  the  synthesis  of  the  characteristic  proteids  of  the  blood 
serum  and  those  of  the  different  organs. 

It  is  certain  that  large  ingestion  of  proteid  in  hot  weather 
increases  the  heat  production  with  accompanying  increase  in 
perspiration  (p.  131).  Meat  should  therefore  be  avoided  in 
hot  weather.  In  cold  weather  such  an  extra  heat  production 
may  produce  a  pleasurable  sensation  of  warmth.  Dr.  Folin,  in 
personal  conversation  with  the  writer,  said  that  a  dietary  of 
carbohydrates,  fat  and  low  proteid,  was  easily  borne  by  a 
coachman  during  the  summer,  but  during  the  winter  the  man 
complained  of  his  sensitiveness  to  cold  when  taking  the  same 
diet. 

Ranke^  describes  experiments  on  himself  (weight  =73 
kilograms)  during  the  hottest  months  of  summer  weather  in 
Munich,  at  which  time  he  partook  of  an  ample  diet,  rich  in  pro- 
teid (135  grams),  containing  3300  calories, — a  diet  which  he 

*  Jaffe:  U.  S.  Department  of  Agriculture,  Bulletin  No.  132. 

*  Abderhalden :  "Zentralblattflird.  gas.  Physiol.  undPath.  d.  Stoffwechsels," 
1906,  Bd.  i,  p.  225. 

'  Ranke:  "Zeitschrift  fiir  Biologie,"  1900,  Bd.  40.  p.  299. 


184  SCIENCE    OF   NUTRITION. 

had  enjoyed  during  the  preceding  winter.  He  had  to  force 
himself  to  eat.  He  was  first  attacked  by  catarrh  of  the  stomach, 
from  which  he  recovered  by  dieting,  and  subsequently  became 
infected  by  diphtheria.  He  had  formerly  suffered  from  catarrh 
of  the  stomach  while  residing  in  the  tropics.  The  excess  of  food, 
and  especially  of  proteid,  threw  an  unnecessary  burden  upon 
the  heat-regulating  apparatus  which  would  not  have  taken  place 
had  the  dictates  of  the  appetite  been  allowed  full  sway  and  had 
the  ration  voluntarily  been  reduced. 

From  the  knowledge  at  hand  there  appears  to  be  no  strongly 
substantiated  argument  why  that  portion  of  mankind  living  in 
a  cool  chmate  should  not  follow  the  general  custom  of  taking  a 
medium  amount  of  proteid  in  moderate  accordance  with  the 
dictates  of  their  appetites.  Everyone  knows  that  excessive 
ingestion  of  highly  flavored  meats  results  in  jaded  appetite,  an 
automatic  signal  of  excess. 

A  similar  excess  of  food  when  given  to  dogs  results  in  vomit- 
ing. Rubner^  says  that  many  years  of  experience  with  dogs 
leads  him  to  believe  that  appetite  and  capacity  for  digestion  and 
absorption  depend  on  the  dog's  requirement  for  energy  in  his 
given  state  of  nutrition.  A  diet  which  a  dog  will  greedily  devour 
when  in  a  room  at  a  temperature  of  0°,  he  will  in  part  refuse 
when  at  a  temperature  of  33°. 

While  the  proteid  quantity  in  the  diet  may  vary  within 
wide  limits  with  the  taste,  the  purse,  or  the  fad  of  the  individual, 
the  quantity  of  calorific  energy  required  by  the  organism  is  a 
remarkably  constant  factor,  being  35  calories  per  kilogram  of 
body  weight  in  the  average  man  doing  light  work  on  a  mixed 
diet.     Comparatively  little  of  this  energy  is  furnished  by  proteid. 

In  a  fasting  individual,  proteid  furnishes  13  and  fat  87  per 
cent,  of  the  total  heat  given  off  from  the  body. 

In  Yoit's  medium  mixed  diet  designed  for  a  laboring  man, 
the  118  grams  of  proteid  furnishes  about  15  per  cent,  of  the  total 
of  3055  calories. 

In  such  an  experiment  as  Siven's,  mentioned  on  page  178, 

'  Rubner:  "  Energiegesetze,"  1902,  ^.  83. 


A   NORMAL   DIET.  1 85 

which  represents  the  lowest  possible  level  of  nitrogen  equilibrium, 
the  25  grams  of  proteid  ingested  furnished  loo  calories  out  of 
2717  ingested  in  the  food,  or  3.6  per  cent.  However,  since  the 
total  metabolism  was  measured  as  2082  calories,  the  proteid 
furnished  approximately  5  per  cent,  of  this  energy. 

Chittenden  ^  gives  a  dietary  containing  50  grams  of  proteid 
and  2500  calories  as  sufficient  for  a  soldier  at  work.  This 
allows  8  per  cent,  of  the  total  energy  in  proteid.  These  data 
may  be  thus  summarized: 

Cal.  from  Pro-    Cal.  from  Fat  and 
Grams  of  Pro-        teid   Metabo-     Carbohydrate  Me- 
TEiD  IN  Diet.  lism  in  per  tabolism  in  per 

CENT.  CENT. 

Starvation o  13  87 

Voit's  standard  (lib- 
eral proteid) 118  15  85 

Chittenden's    standard 

(reduced   proteid)  50  8  92                 ' 

Siven's  minimum 25  5  95 

The  calories  other  than  those  contained  in  proteid  may  be 
given  as  carbohydrates  or  as  fat.  Voit  allows  a  laborer  500 
grams  of  starch  (2050  calories)  as  the  quantity  which  the  in- 
testinal canal  may  readily  digest,  and  adds  56  grams  of  fat  (521 
calories)  to  the  diet. 

It  has  already  been  observed  that  half  the  calories  may  be 
given  as  fat  and  half  as  carbohydrates  without  affecting  the 
carbohydrate  power  of  economy  over  the  proteid  metaboUsm 

(P=  157)- 

This  part  of  the  subject  really  becomes  a  mere  matter  of 
calculation  of  the  requirement  of  the  resting  organism,  and  the 
addition  thereto  of  sufficient  energy  to  accomphsh  the  mechani- 
cal work. 

How  this  is  done  has  already  been  set  forth  in  another  chap- 
ter. A  bicyclist  riding  for  sixteen  hours  may  have  a  metabohsm 
amounting  to  9000  calories  daily,  and  the  average  ration  of  a 
Maine  lumberman  may  rise  to  a  value  of  8000  calories.  Cham- 
pion wrestlers  in  a  world's  contest^  may  ingest  daily  during  their 

^  Chittenden:  Loc.  cit.,  p.  254. 

^  Lavonius:  "Skan.  Archiv  fiir  Physiologie,"  1905,  Bd.  xvii,  p.  196. 


1 86  SCIENCE    OF    NUTRITION. 

periods  of  effort  diets  containing  proteid  21 7.9  grams  (35.1  grams 
of  N);  fat,  259.5  grams;  carbohydrates,  431  grams;  together, 
5070  calories:  or  proteid,  182.2  grams  (29.2  grams  N);  fat,  204.6 
grams;  carbohydrates,  392.3  grams;  together,  4254  calories. 
Much  cream  was  taken  by  these  last-named  individuals. 

Chittenden^  has  fallen  into  error  in  the  commendation  of 
2500  to  2600  ca/lorics  as  an  ample  diet  for  a  soHder  at  drill. 
For  himself,  pursuing  a  sedentary  life,  Chittenden  prescribes 
2000  calories  or  35  per  kilogram,  while  JMendel  requires  2448 
calories,  or  35.3  calories  per  kilogram.  These  are  entirely 
normal  values  for  people  at  light  work.  In  the  earliest  calcula- 
tions of  Voit,  in  1866,  it  was  shown  that  a  man  of  70  kilograms 
on  a  medium  mixed  diet,  produced  2400  calories,  or  34.3  calories 
per  kilogram;  and  Rubner  allows  2445  calories  to  men  of  70 
kilograms  weight  engaged  in  occupations  involving  light  mus- 
cular work, — such  men  as  writers,  draughtsmen,  tailors,  phy- 
sicians, etc.  But  the  soldiers  under  Chittenden  were  put  for 
two  hours  in  the  gymnasium,  then  apparently  drilled  for  one 
hour,  and  walked  another  hour.  This  physical  work  requires 
increased  energy  from  metabolism.  It  has  been  shown  that  to 
walk  2.7  miles  in  an  hour  on  a  level  road  requires  an  increased 
metabolism  of  159.2  calories  in  a  man  weighing  70  kilograms. 
If  a  soldier  during  four  hours  actually  expended  this  equivalent 
mechanical  energy  in  excess  of  the  amount  of  Professor  Mendel 
in  his  laboratory,  then  his  metabolism  would  be  larger  than 
Professor  Mendel's  by  637  calories,  or  he  would  have  a  total 
metabolism  of  3085. 

In  Chittenden's  experiments  there  was  no  analysis  of  the 
expired  air,  and  conclusions  are  drawn  from  the  maintenance 
of  body  weight. 

Several  of  the  larger  sized  soldiers  (those  who  weighed  70 
kilograms)  lost  between  3.5  and  8.5  kilograms  of  body  weight 
during  the  experiments.  Fritz,  weighing  76.0  kilograms,  lost 
3.6  kilograms  in  five  months.  Had  this  all  been  fat,  one  can 
estimate  that  its  heat  value  would  have  been  33,480  calories, 

'  Chittenden:  Loc.  cit.,  p.  254. 


A   NORMAL    DIET.  1 87 

or  an  available  daily  combustion  of  body  substance  equal  to 
223  calories.  Conclusions  drawn  from  weight  alone  can  be  of 
only  the  roughest  character  (see  p.  67). 

For  ordinary  laborers  working  eight  to  ten  hours  a  day — 
such  as  mechanics,  porters,  joiners,  soldiers  in  garrison,  and 
farmers — 3000  calories  does  not  seem  an  excessive  quantity. 

Rubner's  diet  calls  for  2868  calories.  Chittenden's  allow- 
ance (2500-2600)  is  too  low%  while  Atwater's  (3400)  appears 
excessive. 

A  third  class  are  men  at  hard  labor,  such  as  soldiers  in  the 
field,  shoemakers,  blacksmiths,  etc.  For  these  Voit  allows  a 
dietary  containing  3574  calories;  Rubner  3362  calories;  and 
Atwater  4150  calories.  The  differences  in  these  figures  are 
merely  differences  in  the  quantity  of  work  alone. 

In  almost  all  the  rations  given,  carbohydrates  do  not  exceed 
500  grams.     The  remainder  is  made  up  of  fat. 

Woods  and  Mansfield^  report  a  dietary  study  of  a  camp  of 
fifty  Maine  lumbermen  actively  engaged  in  chopping  and  yard- 
ing logs.  The  investigation  continued  for  six  days.  The  daily 
average  ration  per  man  was  as  follows:  Proteid,  164.1  grams; 
fat,  387.8  grams,  carbohydrates,  982.0  grams;  calories,  8083.0. 
This  dietary  would  appear  almost  fabulous  were  it  not  for 
the  fact  that  Atwater  has  actually  shown  that  a  metabolism 
equivalent  to  9300  calories  a  day  may  be  produced  by  a  man 
riding  a  stationary  bicycle  for  sixteen  hours. 

A  lower  ration  than  the  lowest  here  mentioned  may  be 
allowed  to  one  who  is  confined  to  his  bed  (p.  74).  In  many 
hospitals,  however,  it  has  been  found  that  liberal  feeding  of 
the  very  poor  is  often  better  than  medicine. 

The  "standard"  dietaries  are  given  below,  not  because  they 
are  inflexible  requirements  in  any  sense  of  the  word,  but  merely 
for  the  convenience  of  the  reader.  The  individual  standard 
will  ever  be  controlled  by  climate,  the  amount  and  kind  of 
mechanical  effort;  by  appetite,  purse  and  dietetic  prejudice. 

^  Woods  and  Mansfield:  Loc.  cit. 


i88 


SCIENCE   OF   NUTRITION. 


STANDARD  DIETARIES  FOR  A  MAN  OF  70  KILOGRAMS. 

V'OIT.                           RUBNER.  AtWATER. 

Light  work: 

Proteid 123  100 

Fat 46  * 

Carbohydrates 377  * 

Calories 2445  2700 

Medium  work: 

Proteid 118                       127  125 

Fat 56                        52  * 

Carbohydrates 500                       50Q  * 

Calories 3055                      2868  3400 

Hard  work: 

Proteid 145                        165  150 

Fat 100                        70  * 

Carbohydrates 500                       565  * 

Calories 3574                    3362  4150 

♦Carbohydrates  and  fats  to  make  up  the  fuel  value. 

Rubner^  cites  the  following  food  values  consumed  daily  per 
inhabitant  of  different  cities,  based  upon  municipal  statistics  of 
gross  consumption : 

MUNICIPAL  FOOD  STATISTICS. 


Proteid. 

Fat.           Carbohydrates. 

Calories. 

Konigsberg 

84 
96 
98 
98 

31 
65 
64 
60 

414 
492 

465 
416 

2394 
3014 
2903 
2665, 

MunicTi 

Paris 

London 

In  contrast  to  this  comparative  uniformity  hospital  dietaries, 
as  regulated  by  the  management  of  such  institutions,  vary  greatly. 
Rubner^  cites  the  following  hospital  dietaries: 


HOSPITAL  DIETARIES. 


Proteid. 

Fat. 

Carbohydrates. 

Calories. 

Munich 

92 

94 
92 

107 

54 
57 
30 
69 

It;?                      i-j8i 

Augsburg 

222 
393 
533 

1823 
2267 
3266 

Halle 

England... 

It  is  evident  that  the  population  of  a  city  will  sustain  itself 

'  Rubner:  Von  Ley  den's  "Handbuch  derErnahrung,"  1903,  Bd.  i,  p.  160. 
'  Rubner:  Loc.  cit.,  p.  157. 


A  NORMAL   DIET.  1 89 

in  accordance  with  its  needs.  In  public  institutions,  however, 
such  as  poorhouses,  prisons,  asylums,  hospitals,  and  in  military 
and  naval  estabhshments,  scientific  knowledge  of  the  needs  of 
the  individual  becomes  a  very  important  consideration.  The 
prolonged  endurance  of  an  army  of  soldiers  is  just  as  dependent 
on  an  ample  army  ration  as  is  the  battleship  dependent  on  its 
supply  of  fuel.  Not  only  the  quantity  of  the  food  makes  for  the 
well-being,  but  it  must  taste  well.  No  amount  of  actual  fuel 
value  could  compel  the  American  soldiers  of  the  Spanish- 
American  war  to  eat  the  "embalmed  beef"  furnished  by  the 
Government.  The  flavor  is  to  the  man  what  oil  is  to  the  ma- 
chinery of  the  battleship.  Without  flavor  in  the  food  the  diges- 
tive apparatus  does  not  run  smoothly.  In  ordinary  civilized 
life  even  psychical  influences  act.  The  cloth  on  the  table  must 
be  spotless,  and  the  environment  inviting. 

One  takes  as  food  milk,  eggs,  various  meats,  such  as  beef,  veal, 
pork,  mutton,  fish;  also  cereals,  such  as  bread,  rice,  corn,  macaro- 
ni, beans,  and  peas.     Sometimes  alcoholic  beverages  are  added. 

The  calorific  values  of  the  various  nutrient  materials  may  be 
calculated  by  determining  the  composition  of  the  latter  by  analysis 
and  by  multiplying  the  number  of  grams  of  each  constituent  by 
the  factor  which  represents  its  fuel  value  to  the  organism  (p.  40). 

As  a  simple  illustration  of  this  the  following  experiment  of 
Rubner^  may  be  cited.  A  man  weighing  46  kilograms  ate 
nothing  but  eggs  for  two  days,— 22  on  the  first  day  and  20  on 
the  second.  The  22  eggs  contained  1017.4  grams  of  material;  the 
20,  878.8  grams;  an  average  of  948.1  grams  per  day.  Since  100 
grams  of  egg  contain  14.1  grams  of  proteid  and  10.9  grams  of 
fat,  948.1  grams  would  contain  a  daily  allowance  of  133.6  grams 
of  proteid  and  103  grams  of  fat.  If  Rubner's  standard  values 
for  the  energy  content  are  used,  the  result  will  be  as  follows : 

133.6  grams  proteid  X  4.1  =     547  calories. 
103.3  grams  fat  X  9.3  =    .967  calories. 

Total =  1 5 14  calories. 

or  33  calories  per  kilogram. 

^  Rubner:  "Zeitschrift  fvir  Biologic,"  1879,  Bd.  xv,  p.  127. 


190  SCIENCE    OF    NUTRITION. 

This  dietary  of  eggs  was  therefore  nearly  sufficient  for  the 
fuel  requirement  of  this  undersized  individual.  Notwithstand- 
ing the  large  amount  of  proteid  in  the  dietary,  there  was  a  loss 
of  body  proteid  equal  to  7.5  grams  per  day. 

The  results  of  an  exclusive  milk  diet  are  thus  summarized  by 
Rubner:  ^  Milk  (2438  grams)  containing  84  grams  of  proteid  and 
two-thirds  of  the  requirement  of  energy  for  the  individual,  pro- 
duced a  deposit  of  proteid  equal  to  6.7  grams  daily  (p.  158).  To 
cover  a  requirement  of  2400  calories  daily  3410  grams  of  milk 
would  be  needed,  which  contain  140  grams  of  proteid.  For 
a  laboring  man  with  a  requirement  of  3080  calories,  4380  grams 
of  milk  with  180  grams  of  proteid  would  be  necessary. 

It  is  evident  that  milk  with  its  high  proteid  content  is  a  food 
par  excellence  for  the  growing  organism  or  for  the  invalid  conva- 
lescing from  wasting  disease.  It  contains  too  large  an  amount 
of  proteid  for  a  normal  adult.  A  mixture  of  milk,  toast  and 
cream  (creamed  milk- toast)  may  produce  a  "modified  milk"  of 
proper  value  and  easy  digestibility. 

Rubner  finds  that  1500  grams  of  good  white  bread  contain- 
ing 104.4  grams  of  proteid  (  =  75.2  grams  pure  proteid)  will 
maintain  a  workingman  in  nitrogenous  and  calorific  equiUb- 
rium. 

Atwater  and  Benedict"  have  conclusively  shown  that  alcohol 
may  be  used  in  the  economy  in  place  of  isodynamic  quantities  of 
carbohydrates  and  fats.  They  employed  diets  containing  about 
2500  calories  for  a  man  at  rest  and  3500  for  a  man  at  work. 
During  the  alcohol  days  500  of  the  calories  were  suppHed  in  the 
form  of  72  grams  of  alcohol,  or  about  what  is  contained  in  a  bottle 
of  claret.  The  metabolism  of  the  individual  as  expressed  in 
calories  was  unchanged  by  the  addition  of  alcohol  to  the  diet. 
The  alcohol  was  given  in  six  small  doses  and  98  per  cent,  was 
burned  by  the  organism. 

*  Rubner:  Von  Leyden's  "Handbuch  der  Erniihrungstherapic,"  1903,  Bd. 
i,  p.  132. 

^Atwater  and  Benedict:  "Memoirs  of  the  National  Academy  of  Sciences," 
Washington,  1902,  vol.  viii,  p.  231. 


A  NORMAL   DIET. 


191 


The  following  table  shows  the  average  of  experiments  on  a 
resting  individual  which  lasted  23  days: 

INFLUENCE  OF  ALCOHOL  ON  METABOLISM. 


Dura- 
tion IN 
Days. 

In  the  Food  in  Grams. 

Alco- 
hol. 

Cal.  in 
Food. 

Cal.  of 
Metabo- 
lism. 

P^°-      Fat 
TEID.      *^*^- 

Carbohy- 
drates. 

Balance. 

Ordinary 
diet  . . . 

Alcohol 
contain- 
ing diet, 

13 
10 

114 
115 

69 
47 

354 
273 

72.2 

2496 
2488 

2221 
2221 

— 2.0 
-3-8 

On  the  ordinary  diet  33.7  grams  of  fat  were  daily  added  to 
the  body,  and  on  the  alcohol  days  34.1  grams.  These  very 
valuable  observations  make  it  evident  that  alcohol  is  not  a  direct 
cause  of  obesity.  If,  however,  a  young  man  having  acquired 
certain  dietary  habits  at  home,  continues  the  same  dietary 
at  college  and  begins  to  drink  "in  moderation"  besides,  his 
increasing  rotundity  as  he  returns  on  his  vacations  can  be  readily 
explained  by  the  sparing  influence  of  alcohol  upon  the  fat  in 
his  diet. 

A  liter  of  German  beer  contains  3  to  4  per  cent,  of  alcohol 
and  5  to  6  per  cent,  extractives.  It  yields  450  calories  to  the 
body,  only  half  being  derived  from  alcohol,  the  rest  from  the 
dextrin  and  proteid-like  extractives.  Here  is  a  material  whose 
"fattening"  properties  may  be  very  highly  considered. 

All  alcoholic  beverages  are  taken  with  a  twofold  object,— 
first,  the  desire  for  flavor,  and  second,  for  stimulation.  Their 
food  value,  as  above  described,  is  usually  httle  considered.  In 
general  it  may  be  said  that  alcohol  as  a  stomachic  is  valueless 
when  the  gastric  juice  is  normal,  but  is  beneficial  in  cases  of 
hypersecretion,  hypoacidity,  and  loss  of  appetite.  Under  these 
circumstances  small  amounts  of  beverages  containing  5  to  10 
per  cent,  of  alcohol  are  sufficient  for  all  purposes.^ 

'  Zitowitsch:  Abstract  in  "Biochem.  Centralblatt,"  1905,  Bd.  iv,  p.  574. 


192  SCIENCE   OF   NUTRITION. 

The  subject  of  alcohol  could  be  spun  out  into  a  considerable 
story,  but  for  further  details  the  reader  is  referred  to  other 
sources/ 

To  arrange  a  proper  dietary  for  a  given  individual  or  group 
of  individuals  the  very  complete  and  valuable  tables  of  Atwater 
will  be  found  most  practical.  They  are  added  in  an  appendix 
at  the  end  of  this  volume  for  the  benefit  of  the  student  who  may 
desire  to  apply  in  practice  his  knowledge  of  the  general  laws 
of  metabolism. 

Underfed  or  overfed  individuals  may  alike  become  objects 
of  commiseration  and  proper  subjects  for  rehabilitation. 

'  The  Use  of  Alcohol  in  Medicine:  F.  G.  Benedict,  A.  R.  Cushney,  S.  J. 
Meltzer,  Graham  Lusk,  "Boston  Medical  and  Surgical  Journal,"  1902,  vol. 
cxlvii,  p.  31. 


CHAPTER  X. 

THE  FOOD  REQUIREMENT  DURING  THE  PERIOD 
OF  GROWTH. 

In  the  last  chapter  the  average  food  requirement  of  a  normal 
adult  organism  was  discussed.  This  diet,  however,  may  be 
exceeded  in  cases  where  there  is  a  renewal  of  tissue  following 
wasting  disease,  or  where  there  exists  a  development  of  new 
tissue,  as  during  pregnancy,  or  afterwards  during  lactation, 
which  involves  the  growth  of  the  new-bom  infant. 

TangP  has  reported  some  interesting  observations  on  the 
heat  production  which  takes  place  in  the  hen's  egg  incubated 
at  38°-39°.  Tangl  called  this  the  "energy  for  development" 
or  the  "ontogenetic  energy."  His  method  was  to  determine 
the  calories  in  fresh  laid  eggs  and  to  compare  that  amount  with 
the  calories  found  within  the  egg-shell  at  the  moment  of  the 
birth  of  the  chick.  In  this  latter  case  the  chick  and  the  balance 
of  egg-yolk  were  determined  separately. 

The  results  of  these  experiments  showed  that  for  the  devel- 
opment of  one  gram  of  chick  658  small  calories  were  used,  or 
for  the  production  of  one  gram  of  solids  contained  in  a  new- 
bom  chick  3425  small  calories  were  required. 

Farkas^  has  since  shown  that  for  the  development  from  the 
egg  of  one  gram  of  silkworm  larvse  882  small  calories  are  re- 
quired, or  for  one  gram  of  dry  solids,  3125  small  calories, 
figures  which  he  compares  wath  Tangl's  for  the  egg. 

When  the  whole  hen's  egg  is  considered,  Tangl  finds  that 
32  calories  or  35  per  cent,  of  the  amount  of  chemical  energy  in 
the  original  egg  is  deposited  in  the  body  of  the  young  embryo. 
Sixteen  calories  or  17  per  cent,  of  the  original  total  is  used  as 
the  energy  of  development  in  the  production  of  the  young  chick. 

'  Tangl:  "Pfliiger's  Archiv,"  1903,  Bd.  xcviii,  p.  327. 
^  Farkas:  Ibid.,  Bd.  xcviii,  p.  490. 
13  193 


194  SCIENCE    OF    NUTRITION. 

The  balance  or  48  per  cent,  of  the  original  energy  in  the  egg  is 
largely  found  in  the  abdomen  of  the  chick  and  is  absorbed  by 
the  animal  during  the  early  days  of  life. 

It  is  apparent  from  the  above  that  approximately  one-sixth  of 
the  energy  in  a  hen's  egg  is  used  in  the  development  of  a  chick 
whose  body  contains  one-third  the  original  energy  of  the  egg.  The 
other  half  of  the  energy  becomes  available  for  the  chick  during 
the  tirst  days  of  his  life,  through  absorption  from  the  intestinal 
wall. 

Tangl  linds  that  each  egg  loses  in  solids  during  incubation, 
and  that  the  heat  value  of  one  gram  of  such  solids  is  over  9 
calories.  Since  one  gram  of  fat  yields  9.3  calories,  the  natural 
inference  is  that  fat  furnishes  the  energy  for  development. 

Hasselbalch '  had  formerly  shown  that  the  respiration  carried 
on  by  an  egg  indicated  a  respiratory  quotient  Cg^)  amounting 
to  0.677.     This  low  quotient  points  to  the  combustion  of  fat. 

It  is  obvious  from  this  work  that  chemical  energy  derived 
principally  from  the  oxidation  of  fat  is  used  in  the  development 
of  the  embryonic  chick — the  energy  of  ontogenesis.  So,  during 
pregnancy  in  the  higher  animals,  not  only  must  there  be  growth 
of  the  breasts,  the  uterine  musculature,  and  growth  of  the 
embryo  itself,  but  there  must  be  energy  expended  in  maintaining 
the  new  organism.  Hence  the  appetite  of  the  mother  increases 
during  pregnancy.  Magnus-Levy-  finds  an  increased  require- 
ment for  oxygen  on  the  part  of  the  mother  as  pregnancy  pro- 
gresses.    His  table  is  as  follows: 

OxVOEN   IN  C.C. 
PER  MIN. 

Xon-prcgnant 3°2 

Third  month  of  pregnancy ,^-o 

Fourth      "  "  ,'-5 

Fifth  "  "  340 

Sixth         "  "         349 

Seventh    "  "         378 

Eighth      "  "  363 

Ninth        "  "         5'^3 

'  Hasselbalch:  "Skan.  Archiv  fiir  Physiol.,"  1900,  Bd.  x,  p.  353. 

=  Magnus-Lew :  "Zeitschrift  fiir  Gynakologie  u.  Geburtshilfe,"  1904,  Bd. 
lii.  Also  see  Magnus-Levy:  Von  Noorden's  "Handbuch  des  Stoffwechsels," 
1906,  Bd.  i,  p.  409. 


FOOD    REQUIREMENT   DURING   GROWTH.  1 95 

Magnus-Levy  estimates  that  of  the  80  c.c.  additional  oxygen 
required  during  the  ninth  month  of  pregnancy,  only  10  c.c.  are 
used  for  the  metabolism  of  the  fetus,  20  c.c.  for  the  increased 
respiratory  and  heart  activity,  while  50  c.c.  are  for  the  general 
needs  of  the  maternal  organism,  which  has  increased  in  size 
and  weight. 

On  empirical  grounds  von  Winckel^  for  many  years  has 
used  the  following  diet  for  pregnant  women  with,  he  says, 
"excellent  results": 

Proteid 90  grams.  369  calories. 

Fat 27       "  251         " 

Carbohydrates 200      "  820         " 

Total 1440         " 

This  certainly  seems  a  very  low  ration  and  one  hardly  com- 
patible with  furnishing  the  full  calorific  requirement.  The 
dietary  provided  in  the  New  York  Infirmary  for  Women  and 
Children  is  twice  as  large,  being  Atwater's  diet  for  a  woman 
doing  moderate  work.     It  is  as  follows: 

Proteid 100  grams.  410  calories. 

Fat 100       "  930        " 

Carbohydrates 360       "  1476         " 

Total 2816 

Not  the  mere  maintenance  of  the  mother,  but  a  charitable 
contribution  of  reserve  tissue  for  herself  and  offspring  is  here 
effected. 

Some  very  instructive  experiments  have  been  performed  to 
ascertain  the  course  of  the  proteid  metabolism  before  and  after 
pregnancy. 

Zacharjewski^  investigated  the  nitrogen  metaboHsm  of  nine 
pregnant  women.  In  three  primiparas  nourished  on  diets  con- 
taining an  average  of  16.5  grams  of  nitrogen,  there  was  an 
average  daily  retention  of  1.4  grams  in  the  mother's  organism 

'  Von  Winckel:  Von  Leyden's  "Handbuch  der  Ernahrungstherapie,",  1904, 
Bd.  ii,  p.  469. 

'  Zacharjewski:  "Zeitschrift  fiir  Biologic,"  1894,  Bd.  xxx,  p.  405. 


196  SCIENCE   OF   NUTRITION. 

for  thirteen  days  before  parturition.  In  six  multiparas  the  diet 
contained  20.66  grams  of  nitrogen  and  there  was  a  daily  reten- 
tion of  5.122  grams  of  nitrogen  during  the  last  eighteen  days  of 
pregnancy.  The  figures  correspond  to  a  considerable  con- 
struction of  proteid  tissue  within  the  organism.  After  child- 
birth there  was  always  a  loss  of  tissue  nitrogen  by  the  mother. 
In  one  case  nitrogen  equihbrium  was  estabhshed  on  the  fifth 
day,  and  in  another  on  the  fourth.  In  six  cases  the  loss  of  body 
nitrogen  continued  over  a  longer  time.  Zacharjewski  says 
that  the  process  of  involution  of  the  uterus  is  greatest  during 
the  first  five  to  seven  days  after  delivery,  and  the  high  nitrogen 
output  from  the  mother  is  the  result  of  this.  After  the  ehmi- 
nation  which  is  due  to  these  regressive  changes,  there  is  a 
retention  of  nitrogen.  This  is  probably  attributable  to  the 
building  up  of  the  lactic  glands,  for  Slemons^  shows  that  nitro- 
gen equihbrium,  once  established,  was  constantly  maintained 
in  a  woman  who  did  not  nurse  her  child. 

The  complete  record  of  the  nitrogen  elimination  of  a  nursing 
mother,  one  of  Slemons's  cases,  is  here  reproduced.  It  is  espe- 
cially instructive  on  account  of  the  constancy  of  the  quantity  of 
nitrogen  in  the  diet.  The  woman  was  a  negress  who  gave 
birth  to  a  healthy,  vigorous  child. 

During  the  last  days  of  pregnancy  there  was  an  average 
daily  storage  of  2.98  grams  of  nitrogen,  and  for  eight  days  of  the 
puerperium  an  average  loss  of  4.5  grams.  Later,  between 
the  nineteenth  and  twenty-fifth  days  after  birth  there  was  an 
average  daily  storage  of  2.52  grams  of  nitrogen.  This  may 
have  been  for  the  purpose  of  increasing  the  size  of  the  breasts. 
It  must  be  remembered  that  even  during  the  period  of  involu- 
tion an  increase  in  the  lactic  glands  may  have  been  taking 
place  at  the  expense  of  proteid  derived  from  the  uterus.  So 
the  debit  balance  of  nitrogen  during  this  period  may  not  repre- 
sent all  the  proteid  change  taking  place. 

The  mother  had  plenty  of  milk  and  the  baby  gained  an  aver- 
age of  thirty  grams  a  day  during  the  first  forty  days  of  his  life. 
'  Siemens:  "Johns  Hopkins  Hospital  Reports,"  1905,  vol.  xii  p.  121. 


FOOD   REQUIREMENT   DURING   GROWTH. 


197 


Slemons  remarks  that  the  low  proteid  metabolism  as  indi- 
cated by  the  urinary  nitrogen  of  the  period  of  settled  lactation 
is  a  proof  that  there  can  be  no  important  production  of  milk 
fat  from  proteid. 

PROTEID  METABOLISM  BEFORE  AND  AFTER  CHILDBIRTH. 
Weights  are  in  Grams. 


Days    Before    and 
After  Delivery. 


9 

8 

7 

6 

5 

4 

3 

2 

I 

Deliver} 

I 

2 

3 

4 

5 ■ 

6 

7 

8 

19...... 

20 

21 

22 

23 

24 

25 


N  IN  Food.  X  in  Urine 


19. 
20. 
20. 
19. 

II. 

19.8 
18.8 
19.9 

17-3 
18.3 

18.7s 
19. 


20.5 

19.2 

11.9 
16.6 

18. 

10.9 

16.9 

17.1 

II-3 

13-7 

19.2 

13-3 

19.2 

12. 1 

19.2 

14.1 

18.0 

12.3 

14.9 

12.3 

8.0 

"•5 

4.2 

8.4 

7-1 

13-3 

13-7 
19. 

13.2 
15.8 

15.6 

21.8 

I8.I 
16.8 


1 


15-3 

13-3 

9-7 

13-9   I 
II. 4   ! 

15-6  J 


N     IN 

N 

N     IN 

Feces. 

IN  Milk, 

Lochia. 

0-S3 

-- 

3-15 
2.31 

0.15 

1.99 

1.04 

1.61 

1.99 

1. 19 

2.02 

1.05 

1. 14 

2-15 

1.4 

2.02 

0.84 

2.02 

0.28 

1. 18 

1.29 

^•57 

1.6 

1.58 
1.85 
2.03 
1.58 

N 
Balance. 


+8.12 
+2.07 

4-6.57 
—0.77 

—2-95 
+5-39 
-T-6.57 

+4-54 
+5-12 
+2.06 
— 4.00 

—9.66 

—2.79 

— 0-57 

—4-13 

+0.15 

-6.5 

—3-14 

—9.2 

+4-89 
+0-57 
-f3-39 
+4-39 
+0.68 

+3-72 
—0.16 


In  the  above  experiment  it  will  be  noticed  that  the  nitrogen 
of  the  milk  is  small  in  quantity  as  compared  with  the  urinary 
nitrogen.  On  a  strictly  vegetarian  diet  the  relation  would 
change.  Thus  Voit^  found  48.8  grams  of  nitrogen  in  the  milk 
of  a  cow  and  93.7  grams  of  nitrogen  in  her  urine  for  the  same 
period.  Fingerling^  finds  5.97  grams  of  nitrogen  in  the  milk  of 
a  goat  and  in  her  urine  9.48. 

*  Voit:  "Zeitschrift  fiir  Biologic,"  1869,  Bd.  v,  p.  122. 
'  Fingerling:  Ihid.,  1905,  Bd.  xhai,  p.  84. 


198 


SCIENCE    OF   NUTRITION. 


The  influence  of  nutrition  on  the  production  of  milk  has 
been  the  object  of  countless  investigations,  but  unfortunately 
most  of  these  experiments  have  been  conducted  for  commercial 
purposes  on  cows  and  goats.  These  animals,  with  their  funda- 
mental ration  consisting  of  hay,  do  not  allow  of  the  ingestion 
of  simple  foods.  On  the  other  hand  the  milk  supply  of  even  a 
large  bitch  is  very  limited  in  quantity  and  is  with  difficulty 
obtained.  The  writer  is  not  aware  of  any  systematic  obser- 
vations on  the  composition  of  human  milk  as  influenced  by 
food,  although  such  researches  would  seem  of  vast  importance. 

Perhaps  the  most  ^'aluable  research  which  can  to-day  be 
used  is  an  old  one  of  Voit^  upon  a  bitch  weighing  34  kilograms. 
It  confirmed  the  previous  work  of  Kemmerich  and  of  Subotin. 
The  animal  was  given  meat  alone,  meat  and  starch,  meat  and 
fat,  starch  alone,  fat  alone,  and  was  also  starved.  The  influence 
upon  the  milk  secretion  was  found  to  be  comparatively  small. 
The  research  is  a  model  of  completeness,  the  plan  of  which 
could  well  be  copied  in  an  experiment  on  a  human  being. 

A  part  of  the  results  are  given  below : 

INFLUENCE  OF  DIET  ON  THE  COMPOSITION  OF  THE  MILK  OF 
A  DOG  WEIGHING  34  KILOGRAMS. 


Food. 

Milk. 

< 

Z 

Q 

6 
u 

ui 
5 

ui 

a 

< 

h 
Z 

M 

u 

M 

0 

§i 

ui 
S 

z 

in 

< 

0 

z  .• 

1- 

aJ 

cu 

Z 

0 

Z 

D 

< 

OS 

0 

0 
Z 

Z 

0! 
< 

Z 

> 

^ 

X 

z 

0 

z 

L. 

0 

c 

— 

< 

^ 

L. 

*-* 

s 

< 

0 

a. 

< 

3 

Q 

S 

6 

2 

< 

2 

u. 

t/5 

c- 

— 

t/) 

6. 

1000 

300  starch 

34- 

115 

I.I 

8.8 

3' 

9-9 

•J.JO 

2.71 

7  . 

1000 

200  fat 

34- 

144 

1-4 

10.8 

3-8 

99 

7.50 

2.67 

8. 

1000 

200  fat 

34- 

135 

I.I 

11-3 

2.9 

7.4 

8.39 

2-15 

9  . 

Mixed 

diet 

151 

1-4 

139 

3-4 

9.6 

9.22 

2.24 

10  . 

500 

400  starch 

17. 

138 

1.2 

II-3 

3-8 

8.0 

8.19 

2.7S 

II  . 

500 

300  fat 

17. 

168 

1.6 

16.5 

4.2 

10. 1 

9.83 

2.52 

12  . 

Starv. 

149 

1-5 

13-8 

3-9 

9.5 

9.24 

2.65 

13  ■ 

Starv. 

118 

I.O 

12.2 

3-0 

6.7 

10.32 

2.58 

14  . 

.   . 

500  starch 

137 

I.I 

10. 1 

4-3 

7-4 

7-39 

3.11 

16. 

2000 

'68. 

158 

1.6 

16. 1 

4.4 

10.6 

10.17 

2.82 

17  • 

2000 

68. 

161 

1.7 

14.7 

4-7 

10.9 

9.11 

2.9[ 

'  Voit:  "Zeitschrift  fur  Biologic,"  1869,  Bd.  v,  p.  137. 


FOOD    REQUIREMENT    DURING    GROWTH.  1 99 

The  largest  quantity  of  milk  as  well  as  the  richest  in  pro- 
teid  was  obtained  when  meat  or  meat  and  fat  were  ingested. 
Curiously  enough  a  diet  of  500  grams  of  meat  and  300  grams 
of  fat  gave  milk  of  the  same  amount  and  quahty  as  with  2000 
grams  of  meat.  It  is  usually  said  that  a  large  proteid  diet 
stimulates  the  milk  secretion;  but  this  may  also  be  due  indirectly 
to  the  multiphcation  of  the  gland  cells. 

The  milk  sugar  content  was  scarcely  affected  by  the  diet, 
although  a  slight  percentage  increase  was  obser\'ed  after  starch 
ingestion. 

The  fat  content  was  increased  in  stan-ation  to  its  highest 
percentage.  It  was  not  very  greatly  affected  by  adding  fat  to 
a  meat  diet  and  it  was  greatly  reduced  by  giving  carbohydrates. 

The  action  of  fasting  on  the  fat  content  of  milk  is  better 
shown  in  the  herbivorous  goat.  The  writer^  gave  a  milch  goat 
a  constant  diet  of  hay,  commeal  and  bran,  starved  the  animal 
for  two  days,  and  then  continued  the  former  diet.  The  fat  con- 
tent of  the  milk  was  determined.     The  results  were  as  follows: 

Milk  IN  c.c.  FatixG.  Fat  in  per  Cent. 

460 26.50  5.76 

470 25.90  5.52 

•^„Q ^Q    ,  '  »  r  Starvation. 

19S 18.35  9.27  J 

232 18.75  8.08 

298 16.30  5.47 

348 19.40  5-6i 

362 22.30  6.16 

490 27.70  5.66 

In  fasting,  therefore,  the  fat  content  in  the  milk  of  the  herbiv- 
orous goat  approaches  that  contained  in  the  carnivorous  dog. 
With  a  return  to  the  normal  diet  the  fat  content  in  goat's  milk 
is  reduced  to  its  former  level. 

Morgen,  Beger  and  FingerHng-  find  that  a  diet  rich  in  carbo- 
hydrate and  poor  in  fat  produces  a  poor  cow's  milk  containing 
little  fat,  although  the  general  condition  of  the  animal  remains 

^  Lusk:  "Zeitschrift  fiir  Biologie,"  1901,  Bd.  xlii,  p.  42. 
'  Morgen,  Beger  and  Fingerling:   "Landw.   Versuchsstationen,"    1904,  Bd. 
Ixi,  p.  I. 


200  SCIENCE   OF   NUTRITION. 

perfect.  Addition  of  proteid  increases  the  quantity  of  the  milk 
without  changing  the  low  fat  percentage.  Replacement  of 
some  of  the  carbohydrate  with  isodynamic  quantities  of  fat,  up 
to  0.5  to  i.o  gram  per  kilogram  of  animal,  largely  increased  the 
fat  content  of  the  milk  and  thereby  its  nutritive  value. 

It  has  long  been  known  that  ingested  fat  may  appear  in  the 
milk  of  an  animal.  Quite  recently  Gogitidse  ^  has  shown  that 
after  giving  linseed  oil  to  sheep  their  milk  fat  may  contain  t,t, 
per  cent,  of  linseed  fat.  He  also  finds ^  that  the  fat  of  linseed  oil 
passes  readily  into  human  milk,  and  that  the  fat  of  hempseed, 
while  influencing  the  composition  of  the  milk,  greatly  depresses 
lactation  during  the  period  of  its  ingestion. 

How  may  these  various  effects  of  diet  be  explained?  The 
subject  requires  a  knowledge  of  the  processes  going  on  in  the 
lactic  gland  and  these  are  not  certainly  known.  It  has  been 
generally  believed  that  the  cells  of  the  lactic  glands  undergo  a 
fatty  metamorphosis  and,  themselves  breaking  up,  pass  into  the 
milk  (Voit,  Heidenhain).  The  milk  under  these  circumstances 
might  be  regarded  as  the  substance  of  an  organ,  made  fluid. 

Schafer,^  however,  believes  the  process  to  be  one  of  secretion 
similar  to  that  in  the  salivary  glands,  where  the  cells  prepare 
the  special  constituents  and  pass  them  on  to  the  lumen.  Thus 
casein,  hke  ptyalin,  may  be  specially  elaborated  within  gland 
cells. 

If  this  be  the  true  explanation,  the  influence  of  food,  in  the 
writer's  opinion,  may  be  readily  explained.  An  increased  pro- 
teid ingestion  furnishes  the  digestive  products  of  this  sub- 
stance in  liberal  quantities  and  may  increase  the  activity  of  the 
gland. 

The  milk  sugar  content  of  the  milk  remains  remarkably 
constant.  Cremer,^  for  example,  has  shown  that  the  percentage 
of  milk  sugar  in  the  milk  is  unchanged  in  the  cow  after  dimin- 

*  Gogitidse:  "Zeitschrift  fiir  Biologic,"  1904,  Bd.  xlv,  p.  365. 
'  Gogitidse:  Ibid.,  1905,  Bd.  xlvi,  p.  403. 

^  Schafer:  "Text-book  of  Physiology,"  1898,  vol.  i,  p.  667. 

*  Cremer:  "Zeitschrift  fiir  Biologic,"  1898,  Bd.  xxxvai,  p.  78. 


FOOD   REQUIREMENT   DURING    GROWTH.  20I 

ishing  the  sugar  content  of  the  animal  by  inducing  phlorhizin 
diabetes. 

To  explain  the  fat  content  of  the  milk,  the  writer  offers  the 
following  theory:  When  for  any  reason  sufficient  sugar  does 
not  burn  in  the  body  cells,  these  sugar-hungry  cells  attract  fat. 
It  has  already  been  seen  that  glycogen  and  fat  content  of 
the  liver  are  mutually  antagonistic.  Before  lactation  sets  in, 
the  cells  of  the  mammary  glands  burn  sugar  and  there  is  no 
great  attraction  for  fat.  Milk  sugar  cannot  be  formed  in  any 
great  quantity  before  parturition,  because  it  occurs  in  the  urine 
only  post-partum.^  But  when  in  the  process  of  lactation  the  dex- 
trose furnished  by  the  blood  is  converted  into  milk  sugar 
(which  cannot  be  burned  within  the  organism),  the  lactic  cell 
becomes  a  sugar-hungry  cell  which  at  once  attracts  fat  from  the 
blood.  This  theory  of  the  writer  explains  the  production  of 
milk  fat  by  the  process  of  infiltration.  The  variation  of  the 
percentage  of  fat  in  the  milk  may  be  explained  by  the  quantity 
of  fat  in  the  blood.  During  starvation  the  blood  becomes  rich 
in  fat  on  account  of  the  transportation  of  tissue  fat  to  the  cells. 
A.dministration  of  sugar  at  once  reduces  the  supply  of  fat  in  the 
blood.  But  if  fat  be  ingested  with  carbohydrates  the  blood 
becomes  rich  with  this  fat  and  affords  material  for  a  rich  milk. 

Administration  of  good  cream  with  a  substantial  mixed  diet 
is  highly  to  be  recommended  for  nursing  mothers.  The  daily 
production  of  a  Hter  of  milk,  which  has  a  value  of  640  calories, 
indicates  the  necessity  of  no  small  addition  to  the  daily  ration, 
if  the  woman  is  to  bear  satisfactorily  the  strain  of  lactation. 
Probably  this  extra  nourishment  is  best  given  in  the  form  of 
fat.     Beer  is  also  said  to  increase  the  fat  content  of  the  milk." 

Should  the  fat  of  the  milk  disagree  with  the  infant,  the 
trouble  may  be  due  to  the  kind  of  fat  ingested  by  the  mother. 
If,  however,  the  indigestion  be  due  to  a  large  percentage  of  fat, 
a  carbohydrate  diet  will  reduce  the  percentage  in  the  milk. 

'  Lemaire:  "Zeitschrift  fiir  physiologische  Chemie,"  1896,  Bd.  xxi,  p.  442. 
^  Temesvarv:  "  Centralblatt  fiir  die  med.  Wissenschaften,"  1900,  Bd.  xxxviii, 
p.  688. 


202  SCIENCE    OF   NUTRITION. 

A  very  important  fact  regarding  the  nutrition  of  the  young 
is  that  the  milk  of  one  race  is  specifically  adapted  to  the  growth 
of  the  offspring  of  that  particular  race.  Bunge '  found  that  dog's 
milk  had  an  ash  of  exactly  the  same  composition  as  the  ash  of 
the  new-born  puppy.  The  ash  of  the  milk  was  therefore  per- 
fectly adapted  for  the  construction  of  new  puppy  tissue.  It 
was,  however,  entirely  different  in  composition  from  human,  or 
cow's,  or  other  milk.  Only  in  the  case  of  iron  is  the  quantity 
lower  than  corresponds  to  the  composition  of  the  offspring, 
but  this  factor  is  offset  by  the  fact  that  the  animal  when  new- 
born is  richer  in  iron  than  it  is  at  any  other  period  of  life.  Not 
only  this,  but  the  casein  of  the  different  milks  is  different  in 
chemical  behavior.  And  besides  this,  the  rennin  of  the  stom- 
ach is  said  to  be  specifically  adapted  for  the  coagulation  of  the 
casein  produced  by  the  female  of  the  same  race.' 

Furthermore,  the  percentage  quantity  of  the  constituents  in 
the  milk  is  dependant  upon  the  rapidity  of  the  growth  of  the 
organism.  Bunge ^  has  shown  this  in  the  following  comparative 
table : 

Time  is  Days  for 
THE  New-born 
Animal  to  ioo  Parts  of  Milk  Contain 

Double  its  Weight.  Proteid.  Ash.         Calcium  Oxide. 

Man i8o  1.6  0.2  0.0328 

Horse 60  2.0  0.4  0.124 

Calf 47  3.5  0.7  0.160 

Kid iQ  4.3  0.8  0.210 

Pig 18  5-6 

Lamb 10  6.5  0.9  0.272 

Dog 8  7.1  1.3  0.453 

Cat 7  9.5  ..                    

Camerer^  finds  that  human  milk,  drawn  three  to  twelve 
days  after  parturition,  contains  0.2  milligram  of  iron  (Fe,©,) 
per  100  c.c,  while  the  later  milk  contains  o.i  milligram.  The 
quantity  is  decreased  if  the  environment  or  the  condition  of  the 

^  Bunge:  "Zeitschrift  fiir  Biologie,"  1874,  Bd.  x,  p.  326. 

^  Kiesel:  "Pfliiger's  Archiv,"  1905,  Bd.  cviii,  p.  343. 

'Bunge:  "Lehrbuch  der  physiologische  Chemie,"  1898,  p.   118. 

^  Camerer:  "Zeitschrift  fiir  Biologie,"  1905.  Bd.  xlvi,  p.  371. 


FOOD    REQUIREMENT   DURING    GROWTH.  203 

mother   be   poor.^     Using    the    customary  methods  of  infant 
feeding  with  cow's  milk,  the  infant  obtains  too  Httle  iron. 

Blauberg^  reports  the  following  percentage  absorption  of 
the  ash  of  cow's  and  human  milk: 

Per  Cent.  Milk 
Kind  of  Milk,  Subject.  Ash  Absorbed, 

Cow's Infant.  60.70 

Diluted  cow's "  53-72 

Human "  79-42 

Human "  81.82 

Cow's Adult.  53-20 

The  quantity  of  calcium  in  cow's  milk  is  in  excess  of  the 
needs  of  the  human  infant. 

The  absorption  of  the  energy- containing  constituents  of  the 
milk  is  remarkably  constant.  This  is  illustrated  in  the  follow- 
ing table  made  from  Rubner's  experiments^  which  show  the 
physiological  utilization  of  the  total  calories  of  milk : 

Per  Cent,  of  Calories 
Absorbed, 

Human  milk g  r  .6  to  94.0 

Diluted  cow's  milk 90.7 

Diluted  cow's  milk  +  milk  sugar 92.2 

Same  given  to  stunted  infant 87.1 

Cow's  milk  given  to  an  adult 89.8 

As  regards  the  relative  composition  of  average  cow's  and 
human  milk  five  and  a  half  months  after  parturition,  the  fol- 
lowing comparison  may  be  made. 

PERCENTAGE    COMPOSITION    OF    COW'S   AND    HUMAN  MILK. 

Cow's*  HUMAN.5 

Proteid 3.41  i.o 

Fat 3.65  3.0 

Milk  sugar 4.81  6.4 

'  Jolles  and  Friedjung:  "Arch,  fiir  experimenteUe  Path,  und  Pharm.," 
1901,  Bd.  xlvi,  p.  247. 

^  Blauberg:  "Zeitschriftfiir  Biologie,"  1900,  Bd.  xl,  p.  44. 

^  Rubner:  Ibid.,  1899,  Bd.  xxxviii,  p.  380.  For  further  statistics  of  absorp- 
tion consult  Tangl:  "Pfliiger's  Archiv,"  1904,  Bd.  civ,  p.  453. 

*  Rubner:  Von  Leyden's  "Handbuch,"  1903,  Bd.  i,  p.  95. 

'Rubner  and  Heubner:  ' ' Zeitschrif t  fiir  ex.  Pathologie  und  Therapie," 
1905,  Bd.  i,  p.  I. 


204  SCIENCE   OF   NUTRITION. 

Or,  expressed  in  the  relative  calorific  value  of  the  different 
constituents  this  comparison  may  be  given:' 

PERCENTAGE    DISTRIBUTION    OF    CALORIES  IN   COW'S    AND 
HUMAN  MILK. 

Cow's.  Human. 

Proteid   21.3  7.4 

Fat 49-8  43-9 

Milk  sugar 28.9  48.7 

Here,  then,  there  are  tremendous  differences  of  composition 
which  forces  the  conclusion  that  cow's  milk  is  not  to  be  sub- 
stituted for  human  milk  in  rearing  a  child. 

Patein  and  DavaP  find  that  human  milk  after  the  first 
month  of  lactation  contains  but  0.8  to  i  per  cent,  of  casein. 

Another  distinction  between  cow's  and  human  milk  is  that 
the  former  contains  but  little  extractive  nitrogen  while  the  latter 
may  contain  18  to  20  per  cent.^  This  is  probably  one  of  the 
causes  of  the  increase  of  the  ^•-  ratio  (p.  36)  to  over  one  in  the 
urine  of  breast-fed  infants. 

The  large  proteid  content  of  cow's  milk  may  be  evil  for  the 
child.  In  the  first  place  it  clots  in  a  heavy  mass  in  the  baby's 
stomach ;  and  in  the  second  place,  even  though  it  be  digested,  it  is 
relatively  much  above  the  requirement  of  the  organism,  and  its 
specific  dynamic  action  increases  the  amount  of  heat  produced. 

If  cow's  milk  be  diluted  with  two  or  more  parts  of  water,  its 
proteid  content  may  approach  that  of  human  milk  and  its  pre- 
cipitation by  rennin  in  the  stomach  is  in  the  form  of  flakes. 
This  precipitation  of  cow's  casein  takes  place  in  even  finer 
flakes  when  the  milk  is  mixed  with  barley  water,  as  was  shown 
by  Chapin. 

Chapin's  observations,  in  which  the  writer  assisted,  have 
been  confirmed  by  White,*  who  says  that  this  action  is  due  to 
the  presence  of  three-fourths  to  one  per  cent,  of  dissolved  starch. 

'  Rubner:  "Energiegesetze,"  IQ02,  p.  418. 

'Patein  and  Daval:  "Journal  de  Pharm.  et  de  Chemic,"  1905,  T.  21,  p.  193. 
^Rubner  and  Heubner:  Loc.  cit. 

*  White:  "Journal  of  the  Boston  Society  of  Medical  Sciences,"  1900,  vol. 
V,  p.  13c. 


FOOD   REQUIREMENT   DURING   GROWTH.  205 

The  dilution  of  cow's  milk,  however,  reduces  the  quantity 
of  fat  and  carbohydrates,  and  these  must  therefore  be  added  to 
the  milk  in  order  to  make  a  proper  diet  for  a  child. 

To  obtain  a  sufficient  fat  content,  "top  milk,"  rich  in  fat, 
may  be  taken  from  milk  which  has  been  standing,  and  may  be 
mixed  with  water.     Milk  sugar  may  then  be  added. 

Such  a  milk  is  called  "modified  milk"  and  infants  are 
brought  up  on  it  with  greater  success  than  was  the  case  when 
undiluted  cow's  milk  was  given. 

Human  milk  has  a  varying  calorific  value  dependent  largely 
on  the  amount  of  fat  present.  Thus  Schlossmann^  finds  the 
calorific  value  per  liter  of  nineteen  samples  of  milk  from  nine- 
teen women  averages  719  calories,  with  a  maximum  of  876 
and  a  minimum  of  567.  The  milks  having  the  largest  fuel 
value  contained  5.2  to  5.1  per  cent,  of  fat,  while  that  having  the 
lowest  contained  only  1.8  per  cent. 

The  amount  of  the  child's  metabolism  is  dependent  on 
his  size.  Rubner  states  that  a  baby  weighing  4  kilograms 
produces  422  calories,  an  adult  weighing  40  kilograms,  2106 
calories.     But  the  metabolism  per  unit  of  area  is  the  same. 

Rubner  and  Heubner^  summarize  their  results  on  the  metab- 
olism of  differentlv  conditioned  children  as  follows: 


Calories  pee  Sq. 
Weight  in  kg.      Meter  of  Surface. 

Infant  of  stunted  growth 3  1090 

"       at  the  breast 5  1006 

"       on  cow's  milk 8  1 143 

"       at  the  breast 10  12 19 


The  metabohsm  in  all  these  cases  was  essentially  the  same 
per  unit  of  area. 

In  the  last  case  the  very  noticeable  amount  of  muscle  move- 
ment and  crying  while  the  child  was  in  the  respiration  appa- 


^  Schlossmann:  "Zeitschrift  fiir  physiologische  Chemie,"  1903,  Bd.  xxxvii, 
p.  340. 

^Rubner  and  Heubner:  "Zeitschrift  fiir  ex.  Pathologie  und  Therapie," 
1905,  Bd.  i,  p.  I. 


2o6 


SCIENCE   OF   NUTRITION. 


ratus  increased  the  metabolism.  Further  details  regarding  this 
case  give  a  very  complete  picture  of  the  metabolism  of  an  infant. 
The  child  weighed  4.06  kilograms  at  birth,  and  about  10  kilo- 
grams at  the  time  of  the  experiment  when  five  and  a  half  months 
old.     He  was  given  his  mother's  milk. 

The  first  day  of  the  experiment  the  child  was  very  uncom- 
fortable on  account  of  his  new  environment.  The  last  day  he 
was  given  only  a  small  quantity  of  tea,  and  was  therefore  in 
a  state  of  practical  starvation.  The  carbon  dioxid  excretion  on 
these  days  was  as  follows: 

Grams  of  CO2 
Day.  in  24  Hours. 

First 2  78.8 

Second 219.9 

Third 228.1 

Fourth 231. 1 

Fifth 218.2 

The  diet  on  the  second,  third  and  fourth  days  consisted  of 
1258  grams  of  human  milk  per  day  containing: 

Total  nitrogen i  .99  grams. 

Fat 37.73       " 

Milk  sugar 80.5         " 

Of  the  total  nitrogen  only  i  .63  grams  were  contained  in  true 
proteid,  the  rest  being  in  nitrogenous  extractives.  The  per- 
centage composition  of  this  milk  is  given  on  page  203.  Its 
actual  nutritive  value  was  634.5  calories. 

The  balance  sheet  of  the  respiration  experiment  showed  the 
following  daily  result: 

METABOLISM  OF  AN  INFANT. 


1 

a 

8 

z 

Total 

RETA. 

z 
< 

a 

1 

H 
U 
a 
'•J 

U 

z 

•< 

> 

d 

0 

2 

z 

2^ 

< 
1        » 

z 

z 

< 

C 

S 

z 

;z 

Z« 

Z 

0 

u 

u 

Grams. 

Grams. 

Grams. 

Grams. 

Grams. 

Grams. 

Grams. 

3, 

?,,  4- 

Milk 

1.99 

I-I3 

'     1-53 

4-0.46 

637 

65.8 

— 2.1 

c. 

None 

1. 18 

1. 18 

—1. 18 

-- 

60.8 

—60.8 

FOOD    REQUIREMENT   DURING    GROWTH.  207 

The  infant  was  nearly  in  calorific  equilibrium  during  the 
period  of  milk  ingestion.  There  were  634.5  available  calories 
in  the  milk  and  660.5  calories  produced  in  the  metabolism. 

The  quantity  of  the  proteid  metabolism  was  extremely 
small,  being  9.6  grams  according  to  the  usual  method  of  com- 
putation. The  milk  contained  proteid  to  the  extent  of  7  per 
cent,  of  its  total  calorific  content.  Of  this  only  5  per  cent,  was 
metabolized  and  2  per  cent,  was  added  to  the  body.  The 
metabolism  of  an  infant  may  therefore  be  maintained  on  a  diet 
in  which  5  per  cent,  of  the  energy  is  supplied  by  proteid  and 
95  per  cent,  by  fats  and  carbohydrates. 

The  specific  dynamic  action  of  the  milk  was  almost  negli- 
gible, the  metabolism  being  approximately  the  same  during  the 
period  of  feeding  as  during  that  of  starvation.  Curiously 
enough,  the  proteid  metabolism  was  the  same  on  days  of  milk 
ingestion  as  in  starvation. 

This  child  gained  normally  in  weight  before  and  after  the 
respiration  experiment,  but  during  that  time,  struggling  and 
crying  prevented  fat  addition  to  the  otherwise  well- developed 
normal  infant.^ 

W.  Camerer,  Jr.,^  shows  that  a  breast-fed  infant  nine  months 
old  may  ingest  480  calories  in  the  milk,  produce  420  calories  in 
metabolism  and  add  60  calories  to  his  body,  or  15  per  cent,  of 
the  energy  content  of  the  diet.  In  this  case  40  per  cent,  of  the 
proteid  intake  was  added  to  the  growing  organism. 

Rubner  and  Heubner^  have  reported  a  respiration  experi- 
ment on  a  child  seven  and  a  half  months  old,  nourished  with 
modified  cow's  milk.  The  intake  was  682.8  calories,  the 
metabolism  593.2,  leaving  89.6  calories  or  12.2  per  cent,  for 
addition  to  the  child's  organism. 

It  is  remarkable  that  a  child's  intuitive  sense  of  appetite 
should  determine  the  ingestion  of  nutriment  necessary  to  cover 

'  Heubner:  "  Jahrbuch  fiir  Kinderheilkunde,"  1905,  Bd.  Ixi,  Heft  3. 
^  W.  Camerer,  Jr.:  "Zeitschrift  fiir  Biologie,"  1902,  Bd.  xliii,  p.  i. 
^Rubner   and   Heubner:    "Zeitschrift   fiir   Biologie,"    1899,    Bd.    xxxviii, 
P-  345- 


2o8  SCIENCE    OF    NUTRITION. 

the  energy  requirement  of  his  organism,  and  a  small  addition 
for  normal  development.  A  reduction  of  15  per  cent,  in  the 
intake  of  food  would  bring  his  prosperous  growth  to  a  standstill. 

Heubncr'  says  that  the  average  normal  infant  requires  100 
calories  per  kilogram  of  body  weight  for  normal  nutrition  dur- 
ing the  lirst  three  months  of  his  life;  90  calories  during  the 
second  three  months,  and  80  and  less  thereafter.  The  energy 
content  of  the  food  should  never  sink  below  70  calories  per 
kilogram,  which  is  about  the  maintenance  minimum. 

Oppcnheimcr-  first  called  attention  to  the  fact  that  the  growth 
in  grams  of  normal  breast-fed  children  of  the  same  age,  may  be 
nearly  proportional  to  the  quantity  of  milk  ingested.  Here  the 
milk  presumably  had  the  same  calorific  value  throughout  the  ex- 
periment although  this  could  not  be  determined.  The  quantity 
of  milk  taken  at  each  meal  was  found  by  weighing  the  infant  be- 
fore and  after  nursing.     Oppenheimer's  table  is  here  reproduced : 

GROWTH  IX  GRAMS  FOR  i    KG.  MILK. 

Peer's  Oppenheimer's 

Month.  Subject.  Subject. 

1 33-^  95-0 

II 191. 2  201. 1 

III 120.3  1385 

IV 102.6  103-3 

V 57-7  1^0-8 

The  proportion  of  growth  to  milk  given  was  practically  the 
same  during  the  second,  third,  and  fourth  months  of  these 
children's  lives. 

That  the  growth  of  suckling  pigs  may  be  proportional  to  the 
calorific  value  of  the  milk  has  been  shown  by  work  accomplished 
by  Dr.  L.  C.  Sanford  and  Dr.  Margaret  B.  Wilson'  in  the 
writer's  laboratory.  Newly  bom  pigs  of  two  litters  were  reared 
on  skimmed  cow's  milk  and  on  the  same  milk  fortified  with 
two  and  three  per  cent,  of  glucose  or  of  milk  sugar.  The 
experiments  were  continued  from  fourteen  to  sixteen  days.  The 
results  obtained  in  these  experiments  are  thus  tabulated: 

^  Heubner:  "Berliner  klinische  Wochenschrift,"  igoi,  p.  449. 
^  Oppenheimer:  "Zeitschrift  fiir  Biologie,"  1901,  Bd.  xlii,  p.  147. 
^  Wilson:  "American  Journal  of  Physiology,"  1902,  vol.  viii,  p.  197. 


FOOD   REQUIREMENT   DURING   GROWTH. 
GROWTH  OF  SUCKLING  PIGS. 


209 


Wilson. 


Weight  in  grams  when 
born 

Weight  in  grams  when 
killed 

Growth  in  grams 

Growth  in  per  cent. . 
Milk  fed  in  c.c 

Available  calories  fed 
Growth  in  grams  per 

liter  of  milk 

Growth  in  grams  per 

1000  calories  fed  . . 


Seiu. 


1322 


66.8 
10925 
4053 

81 
218 


Lactose. 


1295 

2435 

1 140 

88.1 

1 1005 

5216 

114 
215 


Dex- 
trose. 


Sanford  and  Lusk. 


Skim.       Lactose. 


I4S5 

1000 

2471 
986 
64.4 
9707 

4620 

1246 
264 
26.4 

6826 
2339 

lOI 

38 

213 

114 

1890 

83S 

79-7 
8836 

3736 

95 


73-6 
9481 
3972 

89 


It  is  seen  that  the  growth  of  the  pigs  in  grams  was  directly 
proportional  to  the  calorific  value  of  the  food  to  the  organism. 
The  one  exception  was  that  of  an  ill-nourished  pig  fed  with 
skimmed  milk.  This  was  an  improperly  nourished  animal 
taking  too  little  food  and  remaining  behind  his  fellows  in  normal 
development.  But  that  five  out  of  six  pigs  of  different  litters, 
of  different  sizes  and  differently  fed,  should  have  gained  in 
weight  respectively  213,  214,  215,  218,  and  222  grams  per  thou- 
sand calories  in  the  food  ingested  seems  more  than  a  coincidence. 

A  pig  doubles  in  weight  in  eighteen  days  after  birth.  The  pig 
of  Dr.  Wilson,  brought  up  on  skimmed  milk  with  3  per  cent, 
of  milk  sugar  added,  nearly  doubled  in  weight  in  sixteen  days. 

Comparing  the  fuel  value  of  sow's  milk  and  that  of  the 
skimmed  cow's  milk  to  which  milk  sugar  had  been  added, 
the  following  results  are  significant.  Of  100  calories  in  the 
food  there  are: 

Skim  Milk  +  3  Per 
Sow's  MiLK.i  Cent.  Milk  Sugar. 

Proteid 34.1  36.5 

Fats .52.4  2.5 

Carbohydrates 13.5  61.0 

^  Calculated  from  Konig:  " Zusammensetzung  der  menschlichen  Nah- 
rungsmittel,"  1889,  p.  350. 

14 


2IO  SCIENCE   or   NUTRITION. 

It  is  apparent  from  this  that  normal  growth  of  the  young 
organism  may  be  attained  by  the  replacement  of  fat  by  milk 
sugar  in  isodynamic  quantity.  This  fact  may  become  of  impor- 
tance in  infant  feeding. 

Dr.  Wilson  found  that  when  the  pigs  reared  on  these  diets 
were  killed  and  their  composition  compared  with  that  of  three 
pigs  of  the  same  litter  which  were  killed  at  birth,  there  was  a 
retention  for  growth  of  i8  to  19  per  cent,  of  the  energy  in  the 
food.  This  retention  of  a  definite  nutrient  factor  is  a  necessary 
corollary  to  the  fact  of  the  growth  being  proportional  to  the 
calorific  intake. 

In  children  Camerer  found  15  per  cent.,  Rubner  and  Heub- 
ner  12.2  per  cent,  so  retained. 

The  percentage  of  calcium  (CaO)  in  the  dry  solids  of  the 
pigs  reared  on  the  various  skim  milks  was  8.29,  8.02  and  8.13, 
showing  that  the  absorption  of  calcium  depended  on  the  growth 
of  the  organism,  and  not  on  a  variation  in  the  quantity  ingested. 

Another  instance  which  demonstrates  that  the  young  organ- 
ism may  grow  in  proportion  to  the  energy  ingested  in  the  food, 
is  brought  to  light  by  calculations  based  on  the  work  of  E. 
Rost.^  This  author  gave  meat,  fat  and  bone  ash  to  three  dogs 
of  the  same  litter,  the  experiment  starting  on  the  ninety-eighth 
day  of  their  lives  and  continuing  eighty-eight  days.  The 
writer  has  thus  calculated  the  results: 

Dog.  I.  Dog.  II.  Dog.  III. 

Weight  in  grams  at  Start.. .    3,200  2,200  4,15° 

Weight  in  grams  at  end 6,280  4,620  8,750 

Growth  in  grams 3,o8o  2,440  4,600 

Growth  in  per  cent 96  no  no 

Available  calories  ingested.  24,420  17)3^6  34.276 
Gain  in  grams  per  1000  cal- 
ories ingested 122                   141  T34 

It  is  worthy  of  note  that  these  growing  dogs,  fed  with  meat 

and  fat,  gained  in  weight  nearly  the  same  number  of  grams 

per  1000  calories  ingested  in  the  food.     This  law  of  growth 

seems   reasonably   established.     It   simply   expresses   the   fact 

'  Rost:  "Arbeiten  aus  dem  kaiserlichen  Gesundheitsamte,"  1901,  Bd.  xviii, 
p.  206. 


SCIENCE    OF   NUTRITION. 


211 


that  during  the  normal  development  of  the  young  of  the  same 
age  and  species,  a  definite  percentage  of  the  food  is  retained 
for  growth  irrespective  of  the  size  of  the  individual. 

Bunge^  has  recently  recalled  the  relationship  between  ra- 
pidity of  growth  and  longevity,  as  originally  suggested  by 
Flourens  in  1856.  This  writer  believed  that  if  the  time  of  reach- 
ing the  end  of  growth  be  multiplied  by  five,  the  average  term 
of  hfe  might  be  computed.  This  relationship  may  thus  be 
tabulated : 


TABLE  SHOWING  FLOURENS'  LAW  OF  LONGEVITY. 


Man. . 
Camel . 
Horse 
Cow. . 
Lion. . 
Cat. . . 
Dog... 


Time  in  Days 
FROM  Birth  to 
Double  Birth- 
weight. 


180 

60 

47 

9i 

9 


Time  in  Years 
Until  Full 
Growth. 


Deduced  .Aver- 
age Longev- 
ity IN  Years. 


90-100 
40 

25 
15-20 

20 

9—10 

10-12 


Maximum  Re- 
corded Lon- 
gevity IN 
Years. 


152-169 

100 

50 

60 
20 
24 


Bunge  calls  attention  to  the  fact  that  a  horse  more  often 
hves  to  be  forty  than  a  man  to  be  a  hundred.  Either  the  law 
is  false,  or  man  is  a  too  early  victim  of  an  improper  heredity 
or  environment. 

For  metabohsm  in  boyhood,  see  page  146. 

'  Bunge:  "Pfliiger's  Archiv,"  1903,  Bd.  xcv,  p.  606. 


CHAPTER  XI. 

METABOLISM  IN  ANEMIA,  AT  HIGH  ALTITUDES,  IN 
MYXEDEMA  AND  IN  EXOPHTHALMIC  GOITER. 

In  man  one-thirteenth  part  of  the  body  weight  is  carried  as 
blood  to  the  lungs  at  least  every  minute  and  there  exposed  for 
a  period  of  two  seconds  to  the  action  of  the  alveolar  air.  The 
blood  in  the  capillaries  of  the  lungs  may  be  estimated  as  a  film 
o.oi  miUimeter  in  thickness,  and  150  square  meters  in  area,  or 
nearly  a  hundred  times  the  area  of  the  surface  of  the  body. 
Zuntz  estimates  the  combined  thickness  of  the  alveolar  wall  and 
capillary  wall  at  0.004  mm.  This  is  the  total  distance  sepa- 
rating the  alveolar  air  from  the  blood.  The  gaseous  exchange 
between  the  air  and  the  blood  is  thus  readily  made  possible. 
Complete  deprivation  of  oxygen  results  in  asphyxiation  and 
death. 

The  question  arises.  Will  there  be  any  effect  upon  metab- 
olism if  the  oxygen  supply  for  the  body  be  reduced?  Such  a 
reduction  of  oxygen  available  for  the  tissues  might  be  brought 
about  by  bloodletting,  anemia,  carbon- monoxid  poisoning,  by 
life  on  high  mountains,  or  in  balloons  at  high  altitudes,  or 
in  pneumatic  cabinets  at  reduced  pressure,  or  by  the  artificial 
restriction  of  the  free  influx  of  atmospheric  air  into  the  lungs. 
Any  of  these  methods  if  carried  beyond  a  certain  point  is  known 
to  produce  death. 

It  was  noted  by  Lavoisier  and  confirmed  by  Regnault  and 
Reisct  that  the  respiration  of  pure  oxygen  did  not  increase  the 
metabolism.  Liebig  was  convinced  that  atmospheric  pressure 
was  without  influence,  for  it  was  evident  to  him  that  life  at  the 
sea-level  was  of  the  same  character  as  on  high  mountains.  In 
confirmation  of  these  principles  Zuntz^  has  recently  shown  that 

'  Zuntz:  "Archivfiir  Physiologic,"  1903,  Suppl.,  p.  492. 


METABOLISM  IN   ANEMIA.  213 

if  air  rich  in  oxygen  be  respired,  there  is  an  increased  oxygen 
absorption  lasting  for  about  one  minute,  and  then  the  normal 
quantity  is  absorbed.  The  primary  increase  in  the  quantity 
of  oxygen  absorbed  is  due  to  the  filling  of  the  lungs  with  oxygen 
and  a  further  saturation  of  the  blood  with  it,  processes  which 
are  without  effect  on  tissue  metabolism.  There  is  apparently 
no  retention  of  such  oxygen  within  the  cells  of  the  organism. 

The  consideration  of  the  subject  of  subnormal  oxygen  supply 
may  be  taken  up  with  bloodletting,  which  produces  an  artificial 
anemia.  Bauer  ^  in  Voit's  laboratory,  was  the  first  to  study  this 
systematically  and  found  that  the  immediate  result  of  blood- 
letting in  the  dog  was  an  increased  proteid  metabolism,  but 
that  the  carbon  dioxid  elimination  was  unchanged.  Eighteen 
to  27  per  cent,  of  the  total  blood  in  the  body  was  removed  in 
these  experiments. 

Hawk  and  Gies^  confirm  the  results  of  a  higher  proteid 
metabolism  after  bloodletting. 

Finkler^  in  Pfliiger's  laboratory  withdrew  one-third  of  the 
total  blood  from  a  dog,  thereby  reducing  the  rapidity  of  blood- 
flow  in  the  femoral  artery  by  one-half,  and  yet  there  was  no 
change  in  the  quantity  of  oxygen  absorbed,  and  therefore  of  the 
quantity  of  the  carbon  dioxid  exhaled.  Finkler  noted,  however, 
that  the  quantity  of  oxygen  in  the  venous  blood  grew  constantly 
less  after  repeated  bleedings.  This  indicates  the  inter-relation 
between  the  oxygen  supply  and  the  needs  of  the  tissues.  Under 
ordinary  circumstances  there  are  20  volumes  per  cent,  of  oxygen 
in  the  arterial  blood  of  which  12  volumes  per  cent,  may  return 
as  an  unused  excess  to  the  right  heart.  Repeated  bleedings  by 
Finkler  reduced  this  percentage  in  venous  blood  from  11.80 
per  cent,  to  8.80,  4.06,  and  2.71  per  cent.  The  carbon  dioxid 
content  of  the  blood  remained  unchanged.  This  decrease  in 
the  oxygen  content  of  the  blood  may  stimulate  both  the  heart  and 
respiration  to  compensatory  activity,  although  nothing  resembling 

^  Bauer:  "Zeitschrift  fiir  Biologic,"  1872,  Bd.  viii,  p.  567. 

^  Hawk  and  Gies:  "American  Journal  of  Physiology,"  1904,  vol.  xi,  p.  226. 

^  Finkler:  "Pfliiger's  Archiv,"  1875,  Bd.  x,  p.  368. 


214  SCIENCE   OF   NUTRITION. 

asphyxia  be  present.  While  the  total  heat  production  is  un- 
changed in  anemia  following  bloodletting  (except  as  influenced 
by  increased  cardiac  and  respiratory  activity),  still  it  is  evident 
from  the  diminution  of  oxygen  present  in  venous  blood  that  a 
largely  increased  metabolism  would  not  receive  a  sufficient 
supply  of  oxygen  from  the  blood.  Hence  the  anemic  organism 
is  incapable  of  great  muscular  work  without  quick  exhaustion 
accompanied  by  rapid  respiration  and  heart-beat.  These  lat- 
ter are  further  efforts  of  compensation  for  the  decrease  in  the 
oxygen-carrying  elements  of  the  blood. 

Pettenkofer  and  Voit^  observed  the  metabohsm  in  an  acute 
case  of  leukocythemia  of  four  years'  duration,  and  at  a  time 
four  months  before  the  death  of  the  patient.  There  was  one 
white  to  every  three  red  blood-corpuscles,  a  high  degree  of 
anemia,  and  great  physical  weakness.  The  metabolism  was 
exactly  the  same  as  in  a  normal  resting  man  Uving  under  the 
same  dietary  conditions. 

After  bloodletting  of  any  considerable  magnitude,  lactic 
acid  and,  it  is  reported,  a  small  amount  of  sugar,  appears  in 
the  urine.  Thus  Araki '  found  lactic  acid  in  the  urine  of  rabbits 
which  had  been  bled.  He  also  found  lactic  acid  in  the  urine  of 
rabbits  which  had  been  exposed  to  the  action  of  rarefied  air, 
and  he  found  lactic  acid  and  dextrose  in  the  urine  of  animals, 
the  oxygen-carrying  capacity  of  whose  blood  had  been  dimin- 
ished through  the  respiration  of  carbon  monoxid.  It  should  be 
noticed  in  passing  that  where\^er  lactic  acid  is  formed  in  the 
organism  there  is  a  concomitant  rise  in  proteid  metabolism. 
The  anemic  condition  may  possibly  influence  the  enzyme 
which  normally  breaks  up  lactic  acid,  so  that  its  metabolism  is 
not  effected.  Since  this  lactic  acid  is  a  derivative  of  dextrose, 
its  non-combustion  may  raise  the  proteid  metabohsm  to  a  higher 
level,  just  as  is  the  case  when  sugar  remains  unburned  in  dia- 
betes.   This  is  true  in  spite  of  the  fact  that  the  total  metabolism, 

^  Pettenkofer  and  Voit:  "Zeitschrift  fiir  Biologic,"  1869,  Bd.  v,  p.  319. 
'Araki:     "Zeitschrift     fiir     physiologische    Chemie,"    1894,   Bd.  xix,  p 
424. 


METABOLISM   IN   ANEMIA.  21 5 

as  represented  by  the  heat  of  combustion  of  proteid  and  fat, 
remains  unaltered. 

Another  fact  which  has  been  observed  by  Lewenstein^  is 
that  when  rabbits  are  kept  in  a  bell-jar  at  a  barometric  pressure 
of  300  to  400  mm.  (corresponding  to  5000  to  7500  meters  above 
sea-level)  they  die  on  the  second  or  third  day  and  autopsy 
reveals  extreme  fatty  infiltration  of  heart,  liver,  kidney  and  dia- 
phragm. These  animals  took  no  food.  •  The  cause  of  this  fatty 
change,  in  the  present  writer's  opinion,  was  the  lessened  com- 
bustion of  sugar  or  its  derivative,  lactic  acid,  which  always 
induces  an  abnormal  deposit  of  fat  in  any  sugar-hungry  cells 
(p.  246). 

Kohler^  artificially  compressed  the  trachea  of  rabbits  by 
tying  a  lead  wire  around  it.  The  animals  recovered  from  the 
operation  and  lived  for  four  weeks  in  a  condition  of  dyspnea. 
Appetite,  weight,  urine,  and  body  temperature  remained  normal 
almost  until  the  end.  The  dyspnea  was  apparently  insufficient 
to  affect  the  metabolism.  Increased  respiration  and  heart 
activity  were  effectual  efforts  at  compensation,  so  that  there 
was  no  lack  of  oxygen  in  the  animals.  However,  the  altered 
pressure  in  the  lungs  and  the  prevailing  dyspnea  brought  about 
a  condition  of  stasis  of  which  the  animal  died.  The  secondary 
alterations  were  acute  and  widespread,  and  were  hyperemia 
of  the  lungs,  vesicular  and  intralobular  emphysema  of  the  lungs, 
and  hj^ertrophy  of  both  sides  of  the  heart. 

In  emphysema  of  the  lungs  in  man,  determinations  by  Gep- 
pert  and  by  Speck^  have  shown  that  the  respiratory  exchange 
of  gases  was  entirely  within  normal  limits. 

It  is  evident  from  these  various  citations  that  the  general 
oxidation  of  the  body  is  normally  maintained  in  anemia  and  in 
pulmonary  disease,  provided  the  disturbances  are  not  of  ex- 
treme intensity. 

The  constantly  increasing  use  of  mountain  air  as  a  recuper- 

^  Lewenstein:  "Pfliiger's  Archiv,"  1897,  Bd.  Ixv,  p.  278. 

'  Kohler:  "Archiv  fiir  exper.  Path.  u.  Pharm.,"  1877,  Bd.  vii,  p.  i. 

^  Cited  by  Jaquet:  "Ergebnisse  der  Physiologic,"  1903,  Bd.  ii,  I,  p.  562. 


2l6  SCIENCE    OF   NUTRITION. 

ative  force  for  the  ^vornout  individual  leads  to  the  inquiry 
whether  the  mctabohsm  at  high  altitudes  is  different  from  that 
at  the  sea  level.  For  knowledge  of  this  sort  we  are  principally 
indebted  to  Zuntz  and  his  pupils.  The  study  of  the  subject 
may  be  taken  up  by  using  three  different  methods:  First,  the 
pneumatic  cabinet;  second,  balloon  ascensions;  third,  mountain 
ascents. 

The  relative  composition  of  the  atmosphere  is  the  same  at 
all  distances  from  the  earth's  surface.  Durig  and  Zuntz^  find 
that  the  atmosphere  at  a  height  of  2900  meters  contains  carbon 
dioxid  0.03  per  cent.,  nitrogen  79.11  per  cent.,  and  oxygen  20.86 
per  cent.;  whereas,  at  an  altitude  of  4600  meters  it  contains 
carbon  dioxid  0.03  per  cent.,  nitrogen  79.10  percent.,  oxygen 
20.87  per  cent.  These  are  values  identical  with  each  other  and 
with  those  determined  at  sea-level. 

The  pressure  of  the  atmosphere  varies  with  the  height  from 
the  sea-level  as  appears  in  the  following  table: 


Altitude. 

Barometer 

Ieters. 

Feet. 

Miles. 

IN  Mm.  Hg. 

0 

0 

0. 

760 

icco 

3.281 

0.6 

670 

20CO 

6,«;62 

1.2 

592 

3000 

9.843 

1.9 

522 

4000 

13.124 

2-5 

460 

5000 

16,405 

3-1 

406 

6000 

iq,686 

3-7 

358 

7000 

22,967 

4.4 

316 

8coo 

26,248 

5-0 

297 

Fraenkel  and  Geppert"  placed  a  dog,  Avhich  had  fasted  seven 
days,  under  the  influence  of  greatly  diminished  atmospheric 
pressure  and  found  an  increased  proteid  metabolism  which 
continued  on  the  second  and  third  days.  They  also  suspected 
the  presence  of  incomplete  products  of  combustion  in  the  urine. 
These  results  accord  with  Araki's  investigations. 

Von  Terray^  finds  no  change  in  the  respiratory  activity  of 

^  Durig  and  Zuntz:  "Archiv  ftir  Physiologic,"  1904,  Suppl.,  p.  421. 
'Fraenkel  and   Geppert:  "Ueber  die  Wirkungen  der  verdunnten  Luft," 
1883. 

*  Von  Terray:  "Pfluger's  Archiv,"  1896,  Bd.  Ixv,  p.  440. 


METABOLISM   AT   HIGH   ALTITUDES.  21 7 

dogs  in  air  containing  between  87  and  10.5  per  cent,  of  oxygen. 
When  10.5  per  cent,  of  oxygen  is  present  an  increased  respira- 
tory activity  commences.  With  5.25  per  cent,  of  oxygen  there 
is  every  indication  of  lack  of  oxygen  for  the  tissues,  and  the 
ehmination  of  lactic  acid  in  the  urine  is  pronounced.  The  quan- 
tity of  lactic  acid  eliminated  v^as  greatest  after  the  respiration  of 
an  atmosphere  containing  3  per  cent,  of  oxygen.  The  quantities 
obtained  were  1.206,  1.860,  2.176,  2.300,  2.352,  2.663,  3-020,  and 
3.686  grams  of  lactic  acid  in  twenty-four  hours.  In  these  cases 
we  again  see  the  analogy  of  the  metabolism  to  that  already 
cited  as  having  been  discovered  by  Araki  after  bloodletting  in 
rabbits. 

L.  Zuntz  ^  found  that  when  he  respired  in  a  pneumatic  cab- 
inet, at  an  atmospheric  pressure  of  448  mm.  of  mercury,  that 
there  was  no  change  in  his  respiratory  metabolism  as  compared 
with  the  normal.     The  results  may  be  tabulated  as  follows : 

Pee  Cent.  O2  Respired  Per  Minute. 

IN  Air.  Pressure  in  Mm.  Hg.  O2  c.c.  CO2  in  c.C. 

21  758  mm.  231.25  200.15 

12  448  mm.  238.7  213. 1 

This  latter  experiment  was  done  at  a  pressure  corresponding 
to  a  mountain  height  of  4500  meters.  He  also  showed  that 
variations  in  atmospheric  pressure  within  the  above  limits  had 
no  effect  on  the  metabolism  during  muscular  exercise. 

Von  Schrotter  and  Zuntz  ^  made  two  balloon  ascents  to 
heights  of  4560  and  5160  meters.  Zuntz  showed  an  increased 
oxygen  absorption  of  7  per  cent,  above  that  at  sea-level.  In 
the  case  of  Von  Schrotter  the  increase  was  slight,  except  during 
one  interval  of  shivering  when  a  20  per  cent,  increase  was  re- 
corded. The  authors  attributed  the  shght  rise  in  the  metab- 
olism to  the  increased  work  done  by  the  respiratory  muscles. 
During  the  higher  ascent  sugar  appeared  in  the  urine  of  Zuntz, 
indicating  incomplete  oxidation. 

'  Loewi  and  Zuntz:  "Pfliiger's  Archiv,"  1897,  Bd.  Ixvi,  p.  477. 
'  Von  Schrotter  and  Zuntz:  Ibid.,  1902,  Bd.  xcii,  p.  479. 


2l8  SCIENCE   OF   NUTRITION. 

A  research  of  Zuntz^  on  the  subject  of  mountaineering 
describes  how  he  and  Durig  ascended  to  the  Col  d'Olen  (2900 
meters),  and,  having  remained  there  for  a  week,  passed  upward 
to  a  hut  (4560  meters)  constructed  near  the  summit  of  Monte 
Rosa,  the  highest  mountain  of  the  Alps  after  ]\Iont  Blanc. 
They  hved  in  this  hut  two  weeks  and  a  half.  The  height  of  the 
barometer  was  443  millimeters,  which  indicates  a  quantity  of 
oxygen  amounting  to  12.2  per  cent,  of  an  atmosphere.  On 
the  Col  d'Olen  there  was  no  increase  in  their  metabolism  when 
they  were  resting,  and  there  was  no  increase  in  the  requirement 
of  energy  necessary  to  accomplish  one  kilogrammetcr  of  work. 
This  agrees  with  the  results  of  Biirgi  elsewhere  mentioned 
(p.  175).  At  the  higher  level,  near  the  summit  of  the  mountain, 
the  resting  metaboHsm  increased  at  once  and  permanently  to 
the  extent  of  15  per  cent.  Zuntz  during  a  former  sojourn  had 
noted  an  increase  of  44  per  cent,  in  his  metabolism  when  on  the 
mountain.  Exposure  to  the  sunlight  was  almost  without  effect 
on  the  metabolism.  The  increased  metabolism  was  not  due  to 
cold,  for  it  was  present  when  the  individual  was  in  a  warm  bed 
in  the  hut.  At  sea-level  the  energy  equivalent  of  three  kilo- 
grammeters  is  liberated  in  the  body  in  order  to  lift  one  kilogram 
of  body  substance  one  meter  high.  Here  on  the  snow-fields  of 
Monte  Rosa  Durig  required  the  equivalent  of  4.0  to  4.8,  Zuntz 
5.3  to  6.8  kilogrammeters  of  energy  to  accomplish  one  kilogram- 
meter  of  work.  This  agrees  with  a  former  experiment  of  Zuntz 
when  he  was  living  in  the  same  locality,  in  which  he  found  that 
the  increased  metabolism  necessary  to  effect  one  kilogrammetcr 
of  work  in  climbing  to  be  70  per  cent,  above  the  requirement 
for  the  same  work  at  sea-level. 

That  L.  Zuntz  (see  p.  217)  found  no  increase  in  his  metab- 
olism, either  during  rest  or  work,  when  he  was  in  a  pneumatic 
cabinet  under  an  atmospheric  pressure  of  448  mm.,  is  explained 
by  Durig  and  Zuntz  as  due  to  the  short  length  of  the  experiment. 

Not  only  is  the  metabolism  necessary  to  accomplish  work 
greater  on  high  mountains  than  at  sea-level,  but  the  capacity 

*  Durig  and  Zuntz:  "  Archiv  fiir  Physiologic,"  1904,  Suppl.,  p.  417. 


METABOLISM    AT    HIGH   ALTITUDES.  219 

for  work  is  greatly  reduced.  Schumburg^  found  that  he  could 
accomplish  a  maximum  of  999  kilogrammeters  of  work  in  one 
minute  in  Berlin,  619  when  on  the  Monte  Rosa  glacier,  and  only 
354  kilogrammeters  when  he  was  on  the  top  of  the  mountain. 
The  limit  of  work  on  Monte  Rosa  was  therefore  one-third  what 
could  be  accomplished  in  Berlin. 

Durig  and  Zuntz,  Mosso,  and  others,  have  found  their  res- 
piration to  be  distinctly  of  the  Cheyne-Stokes  character  after  a 
return  to  the  hut  subsequent  to  exercise  in  the  higher  Alps. 
They  found  that  when  they  were  on  Monte  Rosa  a  temporary 
oppression  resulted  if  their  respiration  was  partly  hindered, — as 
in  the  case  of  lacing  their  boots.  Also,  strict  attention  to  a 
definite  task  might  reduce  the  respiratory  activity  to  such  an 
extent  that  anemia  of  the  brain,  accompanied  by  dizziness, 
readily  ensued. 

Workman^  reports  that  normal  sleep  was  impossible  when 
camping  in  the  Himalayas  at  a  height  of  19,358  feet  (nearly 
6000  meters).  When  the  individuals  of  the  party  dozed  they 
were  awakened  gasping  for  breath.  Air  at  this  height  con- 
tains 10  per  cent,  of  oxygen. 

The  ventilation  of  the  lungs  of  Durig  and  Zuntz  while  at 
rest  at  different  altitudes  varied  as  follows : 

Respired  in  Liters  per  Mindte. 

Zuntz.  Durig. 

Reduced  to  760  Mm.      Reduced  to  760  Mm. 
Actual.  Hg.  and  0°  C.  Hg.  and  0°  C. 

Sea-level 4.61-5.03  4.15-4.53  5.00-5.63 

Col  d'Olen 5.97-6.36  3.99-4.16  3.81-5.07 

Monte  Rosa.. 6.86-8.5 2  3-7I-4-88  4.05-4.60 

The  actual  amount  of  inspired  air  appears  to  be  about  the 
same  at  different  altitudes,  an  increased  volume  compensating 
for  increasing  rarefication  of  the  atmosphere. 

The  atmosphere  in  which  one  lives  is  really  the  air  within 
the  alveoli  (Pfliiger).  Durig  and  Zuntz  have  calculated  the  pres- 
sure of  oxygen  and  carbon  dioxid  within  their  alveoli  at  different 

^  Zuntz  and  Schumburg:  "Pfliiger's  Archiv,"  1896,  Bd.  Ixiii,  p.  488. 
^Workman:  "Bulletin  of  the  American  Geographical  Society,"  1905,  vol. 
xxxvii,  p.  671. 


2  20  SCIENCE   OF   NUTRITION. 

levels,  and,  measured  in  terms  of  millimeters  of  mercury,  have 
found  them  to  be  as  follows: 

Pressures  in  Mm.  Hg. 

ZrNTZ  (OF  Berlin).       Durig  (of  Vienna). 

O,  CO2  O2  CO2 

At  home — rest 107  36  109  32 

.'\t  home — ascending  walk 109  t,^  99  37 

On  Monte  Rosa — rest 57  21  53  24 

On  Monte  Rosa — horizontal  walk  ...   60  17  55  21 

On  Monte  Rosa — ascending  walk  ...  63  18  55  24 

It  is  evident  from  a  study  of  the  results  that  muscular  exer- 
cise in  all  these  localities  produces  an  increase  in  the  alveolar 
tension  of  oxgyen  and  a  decrease  in  that  of  carbon  dioxid. 
This  is  brought  about  by  the  stimulation  of  respiration. 

It  will  be  interesting  to  examine  the  evidence  of  the  effect 
of  decreasing  oxygen  tension  on  the  capacity  of  the  blood  in  the 
lungs  to  absorb  oxygen.  The  usually  accepted  doctrine  that 
atmospheric  air,  shaken  with  blood,  will  practically  saturate 
the  hemoglobin  present,  rests  upon  Hiifner's  experiments  with 
carefully  prepared  solutions  of  hemoglobin.  Loewi  and  Zuntz,^ 
however,  show  that  if  normal  blood  be  used  the  saturation  is 
89  per  cent,  at  the  most.  On  the  basis  of  this  newer  work, 
Durig  and  Zuntz  ^  have  calculated  the  saturation  of  the  hemo- 
globin within  the  blood  at  the  different  altitudes.  At  Berlin, 
oxygen  exerting  alveolar  pressures  of  113  and  103  mm.  would 
saturate  the  blood  in  the  lungs  to  the  extent  of  81.9  and  80.5  per 
cent.,  respectively.  On  Monte  Rosa  alveolar  o.xygen  at  pres- 
sures of  57.0  mm.  (Zuntz)  and  53.2  mm.  (Durig)  would  respec- 
tively cause  a  saturation  to  the  extent  of  69.5  and  68  per  cent. 
The  lowest  recorded  oxygen  pressure  in  the  alveoli  was  48.3 
mm.  (Durig),  which  corresponded  to  65.9  per  cent,  of  oxyhemo- 
globin, and  was  accompanied  by  severe  headache.  A  quick- 
ened heart-beat  produced  a  more  rapid  circulation  than  normal. 
The  experimenters  find  no  ground  for  believing  that  there  was 
at  any  time  any  real  oxygen  deficiency  in  any  of  the  important 
tissues  of  the  body.     They  consider  that  their  gradual  ascent 

*  Loewi  and  Zuntz:  "  Archiv  fiir  Physiologic,"  1904,  p.  207. 
^  Durig  and  Zuntz;  Loc.  cil.,  p.  442. 


METABOLISM    AT    HIGH   ALTITUDES.  221 

from  sea-level  prevented  the  usual  disturbances  of  appetite  and 
digestion  which  are  probably  caused  by  anemia  in  the  abdom- 
inal region  (mountain  sickness). 

After  exercise,  however,  Zuntz  and  Durig  noted  qualitative 
changes  in  the  metabolism  indicating  incomplete  combustion. 
This  was  shown  in  the  reduction  of  the  respiratory  quotient 
below  that  of  fat.  The  authors  say:^  "  The  experiments  leave 
no  doubt  that  the  increased  deficiency  of  oxygen  supply,  induced 
by  the  greater  metabolism  of  the  tissue  during  exercise,  is  asso- 
ciated with  the  cause  of  the  increased  requirement  of  energy." 

There  is  no  reference  to  the  presence  of  either  sugar  or  lactic 
acid  in  the  urine  after  exercise  on  Monte  Rosa,  substances 
whose  presence  one  might  suspect.  Loewi^  reports  an  in- 
creased excretion  of  amino  acids  during  mountain  sickness 
or  during  exercise  at  these  high  altitudes. 

It  is  apparent  that  life  at  an  altitude  of  4600  meters  is  on  the 
borderland  between  the  normal  and  the  dyspneic.  Less  work 
can  be  accomphshed,  and  this  at  the  expense  of  a  greater  metab- 
olism, because  of  the  inhibition  of  the  muscle  mechanism 
through  the  accumulation  of  imperfectly  burned  products  of 
metabolism. 

Higher  mountain  ascents  have  been  accomplished  than  the 
one  here  described.  The  celebrated  mountaineer,  Whymper, 
has  ascended  Chimborazo  (6247  meters)  without  suffering 
from  mountain  sickness.  Tolerance  for  highest  altitudes  de- 
pends on  individual  idiosyncrasy,  which  has  been  variously 
attributed  to  differences  in  the  capacity  of  hemoglobin  to  absorb 
oxygen,  to  differences  of  diffusion  power  in  the  alveolar  mem- 
brane, and  to  susceptibiHty  to  cosmic  influences,  such  as  electric 
and  magnetic  phenomena. 

The  discovery  of  Viault^  that  at  an  altitude  of  4000  meters 
the  number  of  red  blood-cells  increased  to  7,000,000  and 
8,000,000  per  cubic  mm.  of  blood  appeared  at  first  to  indicate 

'  Autorenref erat :  "Biochemisches  Centralblatt,"  1904,  Bd.  iii,  p.  285. 

^Loewi:  "Archivfiir  Physiologic,"  1906,  p.  386. 

^  Viault:  "Comptes  rendus  de  I'academie  des  Sciences,"  1890,  T.  cxi,  p.  917. 


222  SCIENCE    OF    NUTRITION. 

a  compensatory  increase  in  oxygen-combining  power  during 
life  in  rarefied  air.  However,  Abderhalden^  has  shown  that 
this  phenomenon  is  due  to  an  expression  of  blood  fluid  from  the 
circulatory  system  and  a  consequent  thickening  of  the  blood, 
for  he  finds  no  change  in  the  total  quantity  of  hemoglobin  in 
animals  of  the  same  species  when  they  are  killed  at  different 
heights.  Only  after  prolonged  residence  at  a  high  altitude  may 
any  increase  in  the  quantity  of  hemoglobin  be  possible.^  Such 
an  increase  has  been  positively  shown  by  Zuntz  and  his  co- 
workers.' 

The  results  of  these  varied  experiments  confirm  the  inde- 
pendence of  the  metabolism  of  variations  in  atmospheric  pres- 
sure as  regards  all  the  customary  habitats  of  mankind.  The 
beneficial  properties  of  mountain  air  may  be  largely  the  same 
as  those  derived  at  watering-places,  /.  e.,  outdoor  life,  cool  air, 
exercise,  diversion  through  change  of  scene,  mental  rest,  and, 
finally,  mental  suggestion  of  benefits  received.  The  dry, 
crisp  air  undoubtedly  benefits  catarrhal  disturbances,  which  are, 
on  the  other  hand,  aggravated  by  the  climate  of  the  seashore. 

In  the  search  for  conditions  which  might  reduce  the  intensity 
of  metabolism,  the  influence  of  the  internal  secretions  of  the 
sexual  glands  has  been  prominently  considered.  Careful 
experiments  of  Liithje,^  however,  show  that  castration  in  dogs 
of  both  sexes  has  no  influence  on  the  metabohsm.  It  is  said, 
however,  that  removal  of  the  ovaries  reduces  for  a  time  the 
number  of  red  blood-corpuscles  and  it  is  suggested  that  ovarian 
insufficiency  may  be  the  cause  of  chlorosis.^ 

The  thyroid  gland  is  a  gland  whose  internal  secretion 
profoundly  affects  the  amount  of  general  metabohsm.  This 
influence  is  apparently  brought  about  by  a  substance  called 

*  Abderhalden :  "Zcitschrift  fiir  Biologic,"  1902,  Bd.  xliii,  p.  443. 
^  Abderhalden:  "Pfliiger's  Archiv,"  1905,  Bd.  ex,  p.  98. 
^  Zuntz,  Loewi,  Miiller,  and  Caspari:  "Hohenklima  und  Bcrgwanderungen 
in  ihrer  Wirkung  auf  den  Menschen,"  Berlin,  1906. 

^Liathje:   "Archiv  fiir  ex.  Path,  und  Pharm.,  1902,  Bd.  xlviii,  p.  184. 
'Breuer  and  v.  Seiller:  "Arch.  f.  ex.  Path,  und  Pharm.,"  1903,  Bd.  1,  p.  169. 


METABOLISM   IN    MYXEDEMA.  223 

thyroidin  which,  when  produced  in  normal  quantities,  main- 
tains the  proper  functions  of  the  nervous  system.  A  subnormal 
production  reduces  the  activity  of  the  nervous  system  and  inci- 
dentally the  quantity  of  metabolism.  An  over-production 
increases  the  irritabihty  of  the  nervous  apparatus  and  raises 
the  metabolism.  Myxedema  is  a  condition  in  which  the  thy- 
roid gland  has  atrophied  and  its  secretion  is  no  longer  available. 
Exophthalmic  goiter  presents  the  opposite  phase,  since  here  a 
superabundance  of  thyroidin  is  believed  to  be  produced.  Symp- 
toms somewhat  akin  to  the  latter  condition  may  be  induced  by 
ingesting  thyroid  extracts  in  normal  animals  and  man. 

Magnus-Levy^  found  the  carbon  dioxid  output  increased 
after  giving  a  normal  man  thyroid  extracts.  Fritz  Voit  -  finds 
the  same  to  be  true  of  a  dog,  and  also  that  more  proteid  is  metab- 
oHzed.  It  is  this  latter  action  which  contraindicates  thyroid 
feeding  in  obesity.  However,  Rheinboldt^  states  that  a  man 
fed  with  thyroid  extracts  may  be  maintained  in  nitrogen  equi- 
librium if  much  proteid  be  allowed  in  the  diet. 

Anderson  and  Bergman  *  have  given  large  quantities  of  thy- 
roid extract  to  a  man  who  was  kept  in  perfect  quiet,  and  no 
increased  output  of  carbonic  acid  was  noticed.  They  attribute 
the  increased  metabolism  which  is  usually  observed  to  the 
increased  muscle  tonus  caused  by  the  highly  irritated  central 
nervous  system.  A  high  metabolism  is  observed  in  cases  of 
exophthalmic  goiter.  Friedrich  Miiller,^  reports  a  case  of  an 
individual  weighing  only  29  kilograms  who  constantly  lost 
weight  notwithstanding  a  daily  diet  containing  68  grams  of 
proteid  with  58  calories  per  kilogram.  Under  such  circum- 
stances there  is  undoubtedly  an  abnormally  .high  destruction  of 
both  proteid  and  fat.  The  increased  proteid  destruction  has 
been   attributed   to   toxic    influence    of  the  thyroid  secretion, 

*  Magnus-Levy :  "Berliner  klinische  Wochenschrift,"  1895,  Bd.  xxx,  p.  650. 
^  Voit,  F. :  "Zeitschrift  fiir  Biologie,"  1897,  Bd.  xxxv,  p.  116. 
^  Rheinboldt:  "Zeitschrift  fiir  klin.  Med.,"  1906,  Bd.  Iviii,  p.  425. 
^Anderson  and  Bergman:  "Skan.  Archiv  fur  Physiologic,"  1898,  Bd.  viii, 
p.  326. 

^Miiller:   "Deutsches  Archiv  fiir  klin.  Medizin.,"  Bd.  li,  p.  361. 


224  SCIENCE    OF   NUTRITION, 

It  may  however  be  caused  by  an  overheating  of  the  muscle  cells 
due  to  great  heat  production. 

In  myxedema  the  metabolism  is  reduced  and  there  is  a  fall  in 
body  temperature,  Anderson '  reports  a  case  of  a  woman  whose 
metabolism  was  as  low  as  1260  calories  or  18.8  per  kilogram: 
after  treatment  for  nine  months  with  thyroid  extracts  the  heat 
production  rose  to  2099  calories,  or  32.3  per  kilogram.  These 
latter  are  normal  values.  The  temperature  rose  with  the  in- 
crease in  metabolism. 

Clonic  convulsions  are  a  symptom  following  thyroidectomy, 
and  during  these  periods  the  temperature  rises.  The  convul- 
sions are  central  in  their  origin,  for  in  the  monkey  they  dis- 
appear on  sectioning  the  nerves. 

It  is  possible  to  explain  the  reduced  temperature  as  due  to 
disturbances  in  the  nerve  mechanism  of  temperature  regulation. 
The  diminished  temperature  of  the  body  would  then  be  an 
influence  in  reducing  the  metabolism  of  the  cells.  This  disease 
is  a  rare  example  of  a  condition  in  which  the  metabolic  processes 
are  permanently  depressed. 

'  Anderson:  "Die  physiol.  Abtheil.  eines  klin.  Aufsatzes  in  Hygiea,"  Stock- 
holm, 1898  (quoted  in  Tigerstedt's  "Lehrbuch  der  Physiologic"). 


CHAPTER  XII. 

METABOLISM  IN    DIABETES    AND  IN  PHOSPHORUS- 
POISONING. 

It  is  said  that  the  sweet  taste  of  diabetic  urine  was  famihar  to 
Susruta,  a  physician  who  Hved  in  India  during  the  seventh  cen- 
tury. The  disease,  then  as  now,  may  have  been  more  prevalent 
among  the  Hindoos  than  elsewhere  in  the  world.  In  Europe 
the  sweet  taste  of  diabetic  urine  was  discovered  by  Thomas 
Willis  in  1674,  but  it  was  not  until  another  hundred  years  that 
Dobson,  in  1775,  showed  that  the  taste  was  due  to  the  presence 
of  sugar.     Subsequently  a  hyperglycemia  was  established. 

Claude  Bernard  found  that  the  stimulation  by  puncture  of 
a  group  of  cells  (the  "diabetic  center")  lying  in  the  medulla  near 
the  floor  of  the  fourth  ventricle,  gave  rise  to  an  excretion  of 
sugar  in  the  urine.  This  experiment  is  the  source  of  the  false 
impression  that  diabetes  is  essentially  of  nervous  origin.  It  is 
called  la  piqure. 

Diabetes  is  a  disease  of  particular  interest  since  it  is  a  depart- 
ure from  the  physiological  condition  involving  the  capacity  of 
the  organism  to  care  for  sugar  in  the  normal  fashion.  All  the 
symptoms  are  due  to  this  one  fact.  No  disease  has  been  more 
thoroughly  investigated.  In  presenting  the  details  to  the  reader, 
it  may  be  remarked  that  the  work  done  is  prophetic  of  possible 
accompHshment  along  scientific  lines  in  the  study  of  disease. 
It  is  typical  of  that  "scientific  medicine"  which  afi^rights  the 
devoted  spirits  of  a  passing  empiricism. 

The  foundation  of  modern  knowledge  on  this  subject  was 
aid  by  von  Mering  and  Minkowski  ^  and  by  Minkowski  ^  alone, 

^  Von  Mering  and  Minkowski:  "Archiv  fiir  ex.  Path,  und  Pharm,," 
Bd.  xxvi,  p.  371. 

-  Minkowski:  Ibid.,  1893,  Bd.  xxxi,  p.  85. 
15  225 


2  26  SCIENCE    OF   NUTRITION. 

who  extirpated  the  pancreas  in  dogs  and  demonstrated  that 
such  animals  became  diabetic. 

The  causes  of  the  appearance  of  sugar  in  the  urine  are: 
(i)  Either  the  organism  cannot  burn  sugar,  which  therefore 
accumuhites  in  the  blood  in  excess  of  the  normal,  and  is  filtered 
through  the  kidney  (diabetes  meUitus,  experimental  pancreas 
diabetes);  or  (2)  some  tissues  may  lose  their  sugar-retaining 
function  so  that  the  normal  regulatory  control  of  the  quantity 
of  blood  sugar  is  lost  or  diminished.  (Bernard's  piqure,  ali- 
mentary glycosuria,  phlorhizin  glycosuria). 

The  stimulation  of  Bernard's  "diabetic  center"  is  only 
effective  in  its  results  when  the  liver  contains  glycogen.'  This 
form  of  glycosuria  cannot  be  obtained  in  a  starving  animal.  It 
is  attributed  to  a  sudden  flushing  of  the  liver  with  blood  and  a 
conversion  of  glycogen  into  sugar,  so  that  hyperglycemia  and 
sugar  elimination  through  the  kidney  follow. 

It  is  reported  that  the  sight  of  a  cat  by  a  dog  confined  in  a 
cage  may  result  in  the  appearance  of  dextrose  in  the  dog's  urine. 
Assuredly  it  may  here  Ix-  surmised  that  great  muscular  activity 
on  the  part  of  the  dog  has  thrown  sugar  into  the  blood  in  exces- 
sive amounts.    A  glycogen-free  dog  would  scarcely  be  so  affected. 

Ahmentary  glycosuria  is  seen  in  normal  animals  and  in  man, 
when  sugar  is  given  in  larger  quantities  than  the  glycogen  regu- 
latory function  can  care  for.  Moritz"  finds  two  grams  of 
dextrose  in  the  urine  of  a  man  after  the  ingestion  of  200  grams. 
Such  an  alimentary  glycosuria  lasts  between  three  and  six  hours. 

Hofmcistcr^  has  discovered  that  the  fasting  organism  is  more 
susceptible  to  alimentary  glycosuria  than  the  well-fed  one. 
He  calls  such  a  condition  "starvation  diabetes."  Evidently  an 
organism  whose  glycogenic  function  has  not  been  used  is  less 
capable  of  protecting  itself  from  an  excess  of  dextrose  than  it  is 
during  normal  nutrition. 


*  Dock:  "Pfliiger's  Archiv,"  1872,  Bd.  v,  p.  571. 

^  Moritz:  "Verhandlungen  des  10  Congresses  fiir  innere  Medizin,"   1891, 
p.  492. 

'  Hofmeister:  "Archiv  fiir  ex.  Path,  und  Pharm.,"  1890,  Bd.  xxvi,  p.  355. 


METABOLISM  IN  DIABETES.  ,  227 

Moritz^  observed  0.2  to  0.3  per  cent,  of  sugar  in  the  urine  of 
four  out  of  six  healthy  people  who  had  partaken  of  a  quantity 
of  sweets  and  champagne. 

Evidently  such  conditions  as  these  are  not  to  be  classed  with 
diabetes  meUitus,  where  there  is  a  fundamental  disturbance  in 
the  sugar-burning  power  in  the  organism.  It  would  be  of  ser- 
vice to  distinguish  between  glycosurias  where  the  sugar -holding 
capacity  of  the  organs  has  been  diminished  or  overstrained,  and 
diabetes  in  which  the  sugar-burning  capacity  has  been  affected. 

A  special  type  of  glycosuria  is  caused  by  phlorhizin  injec- 
tions, as  was  discovered  by  von  Mering.^  Here  the  blood  it- 
self while  passing  through  the  kidney  loses  the  power  of  retaining 
its  normal  sugar  content  and  a  h}^oglycemia  results.  Some- 
times when  the  kidney  is  altered  in  Bright's  disease,  phlor- 
hizin is  ineffective  and  no  glycosuria  follows  its  administration. 
The  renal  character  of  phlorhizin  glycosuria  was  demonstrated 
by  Zuntz*  who  placed  cannulae  in  the  upper  portions  of  the  two 
kidneys  and  injected  phlorhizin  into  the  renal  artery  of  one. 
On  the  injected  side,  sugar-containing  urine  appeared  in  two 
minutes,  and  three  minutes  later  the  kidney  on  the  opposite 
side  yielded  sugar  through  its  ureter.  The  delay  was  due  to  the 
lapse  of  time  necessary  for  the  transportation  of  the  phlorhizin 
by  the  blood  stream  from  the  injected  kidney  to  the  other  one. 
In  this  form  of  glycosuria  sugar  ingested  per  os,  or  subcutane- 
ously,  or  as  formed  in  proteid  metabohsm,  is  all  eliminated  in 
the  urine,  provided  the  quantity  given  does  not  flood  the  organ- 
ism with  sugar.^     In  this  latter  case  part  of  it  can  be  burned. 

Loewi^  has  conceived  the  idea  that  the  blood  sugar  is  nor- 
mally in  a  loose  combination  with  colloid.  This  colloid  sugar 
cannot  pass  through  the  glomerulus.  If,  however,  sugar 
accumulates  in  the  blood  above  the  combining  power  of  the 

^  Moritz:  "  Archiv  fiir  klinische  Medizin,"  1890,  Bd.  xlvi,  p.  217. 
^  Von   Mering:  "  Verhandlungen    des  5  Congresses  flir  innere  Medizin," 
1886,  p.  185. 

^  Zuntz:  "Archiv  fiir  Physiologic,"  1895,  p.  570. 

*  Stiles  and  Lusk:  "American  Journal  of  Physiology,"  1903,  vol.  x,  p.  67. 

'  Loewi:  "Archiv  fiir  ex.  Path,  und  Pharm.,"  1902,  Bd.  xlviii,  p.  410. 


228  SCIENCE   OF  NUTRITION. 

colloid,  then  the  crystalloid  dextrose  readily  passes  through  the 
kidney.  This  condition  exists  in  diabetes  melhtus.  In 
phlorhizin  glycosuria  the  kidneys  break  up  the  colloid  sugar, 
and  the  sugar  may  then  be  ehminated.  Stiles  and  Lusk,  while 
accepting  Loewi's  theory,  have  added  the  hypothesis  that  the 
colloid  sugar  cannot  be  burned.  Phlorhizin  acting  in  the  kid- 
ney will  spht  the  compound  and  permit  the  ehmination  of  sugar. 
Any  free  dextrose  in  the  general  circulation  unites  with  the 
colloid  radical  and  is  protected  from  combustion,  as  is  the  case 
when  five  grams  of  dextrose  are  administered  subcutaneously 
only  to  reappear  in  the  urine  (Stiles  and  Lusk).  If  the  quantity 
of  sugar  in  the  blood  rises  above  this  combining  power,  immunity 
from  destruction  is  lost  and  the  sugar  burns.  Phlorhizin 
glycosuria  is  only  temporary  in  character,  and  subcutaneous 
injections  of  alkaline  solutions  of  the  drug  three  or  four  times 
daily  are  necessary  in  order  to  obtain  constant  results. 

The  character  of  phlorhizin  glycosuria  has  been  dwelt  upon 
because  the  total  metabolism  is  here  identical  with  that  observed 
in  diabetes  mellitus.  It  has  long  been  known  that  diabetics  elimi- 
nate sugar  even  after  all  administration  of  sugar  is  stopped. 
It  has  also  been  generally  recognized  that  proteid  ingestion  tends 
to  increase  the  sugar  output  in  the  urine,  W'hile  fat  has  no  effect. 

A  large  amount  of  information  has  been  collected  concerning 
the  relation  between  the  urinary  nitrogen  and  sugar  ehmination 
in  the  fasting  and  meat-fed  diabetic  organism.  The  dextrose 
to  nitrogen  ratio  (D  :  N)  is  a  key  to  the  problem  of  the  quantity 
of  sugar  which  can  be  derived  from  proteid  metabolism  (p.  112). 

Minkowski*  was  the  pioneer  who  discovered  that  depan- 
creatized  dogs,  whether  fasting  or  fed  with  meat,  showed  a  con- 
stant elimination  of  2.8  grams  of  dextrose  for  each  gram  of  ni- 
trogen in  the  urine.  This  ratio  (D  :  N  ::  2.8  :  i)  was  the  average 
obtained  from  seven  dogs  on  twenty-two  different  days.  The 
lowest  ratio  was  2.62  :  i,  the  highest  3.05  :  i.  Some  other 
operators  have  been  unable  to  obtain  these  ratios.     Pfliiger^ 

'  Minkowski :  "  Archi v  fiir  ex.  Path,  und  Phami.,"  1893,  Bd.  xxxi,  pp.  85,  97. 
'  Pfliiger:  "Das  Glycogen,"  1905,  p.  491. 


METABOLISM  IN  DIABETES. 


229 


finds  a  variable  and  generally  lower  ratio,  and  his  dogs  all  died 
of  abscesses.  Embden's^  ratios  are  all  lower  than  Minkowski's, 
and  are  probably  due  to  incomplete  extirpation  of  the  pancreas. 
The  accuracy  of  Minkowski's  results  is  indicated  by  the  fact 
that  the  ratio  (D  :  N  :  :  2.8  :  i)  may  be  easily  established  by  the 
administration  of  phlorhizin  to  rabbits,  goats,  cats,  and  in  cer- 
tain dogs  whose  kidneys  have  been  somewhat  affected,  as,  for 
example,  by  giving  camphor.  Phlorhizin  acts  first  to  cause  a 
sweeping  out  of  the  excess  of  sugar  in  the  organism,  with  a  sub- 
sequent establishment  of  the  ratio.  (See  table,  p.  235.)  The 
ratios  in  different  animals  are  given  in  the  following  table: 

R.\TIOS  IN  DIABETES  OF  D  :  N  :  :  2.8  :  i. 


Dog  .2 

Dog  .3 

Cat.* 

Goat  .5 

Rabbit  fi 

Day. 

13       « 
3       0 
S  0  K 

z 
5 

K 

2 

z 

a 

OS 

o 

X 

z 

s 
0 

r-l 

a 

Second  day  of  Diabetes 

Third      "               "       

Fourth    "               "        

Fifth       "              "       

Day  unknown 

288 
2.94 
3-09 

2.8 

2-93 
2.80 

2-93 

2-95 
2.90 
2.78 

2.89 

2.69 

The  uniformity  of  the  ratio  as  shown  in  different  animals  is 
very  striking.  One  may  calculate  from  these  results  that  45 
per  cent,  of  the  proteid  molecule  may  be  converted  into  dex- 
trose in  the  course  of  metabolism. 

This,  however,  does  not  complete  the  story  of  the  D  :  N 
ratio,  for  a  higher  ratio  or  3.75  :  i  was  discovered  by  Reilly, 

*  Embden  and  Salomon:  "Hofmeister's  Beitrage,"  1904,  Bd.  vi,  p.  63. 
^Minkowski:  Loc.  cit.,  p.  97. 

^  Jackson:  "American  Journal  of  Physiolog}',"  1902,  vol.  viii,  p.  xxxii. 

*  Arteaga:  Ihid.,  1901,  vol.  vi.  p.  175. 

^  Lusk:  "Zeitschrift  fiir  Biologie,"  1901,  Bd.  xlii,  p.  43. 

*  Reilly,  Nolan,  and  Lusk:  "American  Journal  of  Physiolog}-,"  1895,  vol.  i, 
p.  396. 


230  SCIENCE    OF    NUTRITION. 

Nolan,  and  Lusk^  in  the  urine  of  dogs  with  normal  kidneys 
after  subcutaneous  injections  of  phlorhizin.  This  ratio  was 
subsequently  revised  by  Stiles  and  Lusk"  and  found  to  be 
3.65  :  I.  The  importance  of  this  discovery  was  enhanced  by 
the  finding  of  Mandel  and  Lusk^  that  the  same  ratio  may  exist 
in  human  diabetes  when  the  patient  is  given  a  diet  of  meat 
and  fat.     These  ratios  are  thus  comparable: 


Phlorhizinized  Dog> 

DlABEThS  MeLLITISIN    MaN.' 

3.60 

3.60 

3-65 

3-65 

3.66 

3.66 

3.62 

In  another  place  (p.  112)  it  has  been  shown  that  the  D  :  N 
ratio  does  not  vary  after  the  ingestion  of  sufficient  meat  to  double 
the  quantity  of  nitrogen  in  the  urine;  the  sugar  also  doubles. 
The  sugar  production  is  therefore  proportional  to  the  proteid 
metabohsm,  and,  apparently,  must  be  derived  from  proteid. 

Various  objections  have  been  raised  to  this  statement. 
Other  experiments,  however,  confirm  the  above  proposition, 

Liithje®  gave  nutrose  to  a  depancreatized  dog.  Nutrose 
contains  casein  but  no  sugar.  The  dog  weighed  5.8  kilograms 
and  eliminated  11 76  grams  of  glucose  during  twenty-five  days. 
The  tissues  of  the  dog  could  not  possibly  have  contained  over 
232  grams  of  glycogen  at  the  beginning  of  the  experiment.  The 
source  of  the  sugar  could  not  have  been  the  animal's  store  of 
glycogen,  but  must  have  arisen  from  either  proteid  or  fat. 

Pfliiger^  would  have  it  that  fat  metabolism  is  the  principal 
source  of  sugar  in  diabetes. 

It  has  already  been  shown  that  proteid  breaks  up  into  amino 
acids  in  the  intestines,  and  that  such  amino  acids  when  ingested 

'  Rcilly,  Nolan,  and  Lusk:  hoc.  cit. 

'  Stiles  and  Lusk:  "American  Journal  of  Physiology,"  1903,  vol.  x,  p.  67. 
^Mandel   and  Lusk:   "Deutsches  Archiv  fiir  klin.   Medizin,"    1904,   Bd. 
Ix.xxi,  p.  470. 

*  Loc.  cit.,  p.  77.     (Details,  this  book,  p.  64.) 
'  Loc.  cit.,  p.  479. 

"  Liithje:  "Pflugcr's  Archiv,"  1904,  Bd.  cvi,  p.  160. 
'  Pflijger:  Ibid.,  1905,  Bd.  cvm,  p.  115. 


METABOLISM    IN    DIABETES.  23I 

are  the  equivalent  in  metabolism  of  proteid  itself  (p.  103). 
Are  such  amino  acids  convertible  into  dextrose  ? 

Knopfs  has  shown  that  asparagin  given  to  a  diabetic  dog 
yields  at  least  1.3  grams  of  dextrose  for  each  gram  of  its  nitrogen 
metaboUzed.  Stiles  and  Lusk^  find  that  a  pancreatic  digest  of 
meat,  consisting  of  amino  acids,  when  given  to  a  phlorhizinized 
dog,  yields  2.4  grams  of  dextrose  for  each  gram  of  nitrogen. 
Embden  and  Salomon^  find  that  glycocoll,  alanin  and  asparagin 
increase  the  dextrose  output  in  a  diabetic  dog. 

Halsey  ^  believes  that  the  leucin  complex  but  not  leucin  itself 
will  increase  the  sugar  in  the  urine  of  a  diabetic  dog. 

Pfliiger^  explains  that  the  amino  acids  stimulate  the  fat 
metabohsm  in  the  liver  in  such  a  manner  as  to  insure  a  produc- 
tion "of  dextrose  from  fat.  This  can  hardly  be  correct  for  it 
w^ould  be  a  most  remarkable  arrangement  if  amino  bodies  car- 
ried to  the  Hver  of  a  starving  cat  under  the  influence  of  phlor- 
hizin,  and  the  same  quantity  carried  to  the  same  locality  in  a 
dog  with  pancreas  diabetes,  should  in  both  cases  stimulate 
exactly  the  same  sugar  production  from  fat. 

A  simpler  and  probably  truer  conception  lies  in  the  theory 
of  a  denitrogenization  of  the  amino  acids  by  hydrolysis  within 
the  organism  and  the  subsequent  synthesis  of  the  oxy-acids 
into  sugar  by  the  hver. 

A  substance  Hke  glycocoll  might  thus  be  converted  into  gly- 
collic  acid,  and  this  reduced  to  glycolaldehyde,  a  body  whose 
subcutaneous  injection  leads  to  an  output  of  sugar  in  rabbit's 
urine.®  Alanin  in  like  fashion  would  become  lactic  acid,  and 
this  in  turn  dextrose  (p.  292). 

Von  Noorden  ^  suggests  that  leucin  may  split  into  acetone 

^  Knopf:  " Archiv  fiir  ex.  Path,  und  Pharm.,"  1903,  Bd.  xlix,  p.  123. 

^  Stiles  and  Lusk:  "American  Journal  of  Physiolog}',"  1903,  vol.  ix.  p.  3S0. 

^Embden  and  Salomon:  "Hofmeister's  Beitrage,"  1904,  Bd.  v.  p.  507; 
1904,  Bd.  \'i,  p.  63. 

*  Halsey:  "American  Journal  of  Physiolog}',"  1904,  vol.  x,  p.  233. 

'  Pfliiger:  Loc.  cit.,  p.  187. 

'  Mayer:  "Zeitschrift  fiir  physiologische  Chemie,"  1903,  Bd.  xxxviii,  p.  151. 

''Von  Noorden:  "Journal  of  the  American  Medical  Association,"  October 
28,  1905. 


232  SCIENCE    OF   NUTRITION. 

and  lactic  acid,  the  latter  being  converted  into  dextrose.     These 
reactions  might  be  as  follows : 

1.  CHjNHjCOOH  +  HjO   =    CHjOH  COOH  +  NH3 

GlycocoU.  Glycollic  acid. 

3  CHjOHCOH  =   CsHjjOs 

Glycolaldehyde.  Dextrose. 

2.  CHjCHNHjCOOH  +  H,0  =  CH3CHOHCOOH  +  NHj 

Alanin.  Lactic  acid. 

2CH3CHOHCOOH=    QHi^Os 

Lactic  acid.  Dextrose. 

5-  ^J]3>CH— CHjCHNHjCOOH  +  HjO  +  O  =  ^g3>cO+ 

Leucin.  Acetone. 

CH3CHOHCOOH  +  NH3 

Lactic  acid. 

In  confirmation  of  the  hypothesis  that  lactic  acid  is  con- 
vertible into  dextrose,  it  has  been  found  that  the  ingestion  of 
lactic  acid  in  diabetes  does  increase  the  quantity  of  sugar  in 
the  urine.^  Mandel  and  Lusk^  have  shown  that  ^-lactic  acid, 
which  is  the  normal  lactic  acid  of  the  body,  may  be  completely 
converted  into  dextrose  by  the  diabetic  organism.  It  has  also 
been  found  by  Embden  ^  that  if  normal  blood  be  perfused 
through  a  glycogen-free  liver,  the  sugar  content  of  the  blood  in- 
creases. After  varying  the  procedure  he  concludes  that  the 
normal  blood  contains  substances  which  are  convertible  into 
sugar  by  the  liver.  Such  substances  may  be  lactic  acid,  gly- 
colaldehyde, etc.  It  is  therefore  probable  that  the  course  of 
the  intermediary  metabolism  involving  sugar  production  is  as 
has  been  outhned  above. 

Giving  fat  with  meat  to  a  diabetic  will  not  ordinarily  in- 
crease the  sugar  in  the  urine.  The  writer  has  never  observed 
such  an  increase  in  any  of  the  work  of  his  laboratory.  A  large 
production  of  sugar  from  fat  has  been  elsewhere  reported  *  and 

'  Embdon  and  Salomon:  "Hofmeister's  Beitrage,"  1904,  Bd.  vi,  p.  63; 
A.  R.  Mandel,  "American  Journal  of  Physiology,"  1905,  vol.  xiii,  p.  xvi. 

^Mandel  and  Lusk:  "'American  Journal  of  Physiology,"  1906,  vol.  xvi,  p. 
129. 

^  Embden:  "Hofmeister's  Beitrage,"  1904,  Bd.  vi,  p.  44. 

*  Hartogh  and  Schumm:  "Archiv  fiir  ex.  Path,  und  Pharm.,"  1900,  Bd 
xlv,  p.  II. 


METABOLISM    IN    DIABETES.  233 

Cremer^  finds  that  glycerin  given  alone  will  increase  the  output 
of  sugar  in  the  urine. 

On  giving  meat  in  diabetes  the  fat  metabolism  is  reduced 
as  it  would  be  in  the  normal  organism,  and  yet  there  is  no 
effect  on  the  D  :  N  ratio,  and  therefore  the  latter  cannot  be 
influenced  by  the  quantity  of  fat  burned.  This  is  show^n  in  a 
respiration  experiment  made  by  Mandel  and  Lusk'  on  a  dog 
with  phlorhizin  glycosuria  whose  metabolism  starving  and  after 
meat  ingestion  was  as  follows : 

Calories  Calories  Calories, 

D  :  N.       FROM  Proteid.      prom  Fat.  Total. 

Fasting 3.69  80.2  274.4  354-6 

300  grams  meat.. 3. 55  161. 9  261.7  423-6 

The  proteid  metaboHsm  doubled  when  meat  was  ingested, 
the  fat  metabolism  fell,  but  the  D  :  N  ratio  remained  constant. 

If  a  production  of  dextrose  from  fat  metabohsm  be  possible, 
it  must  be  due  to  a  qualitative  alteration  in  the  metaboHsm  in 
rare  and  special  cases.  A  high  authority,  von  Noorden,'  writes: 
' '  In  all  probability  we  may  even  now  make  the  statement  that 
there  are  a  few  cases  of  diabetes  in  which  more  sugar  is  ex- 
creted than  can  be  accounted  for  by  the  amount  of  carbohydrate 
available,  and  the  maximum  quantity  of  proteid  that  could 
have  been  disintegrated,  and  that  in  these  cases  fat  must  be 
looked  upon  as  the  source  of  the  excess." 

A  question  of  special  interest  is  the  cause  of  the  two  D  :  N 
ratios,  2.8  :  i  and  3.65  :  i.  The  former  represents  a  production 
of  45  per  cent.,  the  latter  one  of  58  per  cent,  of  sugar  from  meat 
proteid.  In  neither  case  can  dextrose  ingested  be  burned. 
It  is,  of  course,  possible  that  the  sugar  production  varies  under 
different  circumstances ;  that  is  to  say,  the  organism  (liver  ?)  may 
be  able  at  times  to  produce  sugar  from  a  certain  class  of  pro- 
teid decomposition  products,  and  at  other  times  not.  Or,  one 
may  adopt  the  hypothesis  of  Mandel  and  Lusk,*  which  assumes 

^  Cremer:  "Miinchener  med.  Wochenschrift,"  1902,  Bd.  x.xii,  p.  944. 

^  Mandel  and  Lusk:  "American  Journal  of  Physiology,"  1903,  vol.  x,  p.  54. 

^  Von  Noorden:  "Diabetes,"  Herter  Lectures,  1905,  p.  80. 

^Mandel  and  Lusk:  "Deutsches  Archiv  fiir  klinische  Medizin,"  1904,  Bd. 
Ixxxi,  p.  491. 


2  34  SCIENCE   OF  NUTRITION. 

a  difference  between  a-colloid  dextrose  and  ^3-colloid  dextrose 
existing  in  the  blood.  By  o-dcxtrose  is  understood  the  amount 
of  dextrose  represented  by  the  ratio  D  :  N  :  :  2.8  :  i,  or  45  per 
cent,  of  the  proteid.  The  /3-dextrose  represents  the  additional 
13.6  per  cent,  of  the  proteid,  when  the  ratio  3.65  :  i  is  present. 
The  ratio  would  depend  on  the  combustion  or  non-combustion 
of  the  ,?-dextrose.  If  the  latter  burns,  it  must  do  so  as  a  com- 
plex, for  as  free  dextrose  it  would  be  eliminated  in  the  urine. 

This  theory  of  a  difference  in  chemical  union  would  explain 
the  fact  discovered  by  Straub^  for  carbon  monoxid  "diabetes" 
and  by  Seelig"  for  glycosuria  following  ether  inhalation,  that 
sugar  appears  in  the  urine  in  large  quantity  if  a  dog  be  fed 
with  meat,  but  disappears  if  the  animal  be  given  carbohydrate 
alone.  Seelig  found  no  glycosuria  when  an  intravenous  in- 
fusion of  oxygen  was  administered  at  the  same  time  that  ether 
was  given.  It  may  be  that  lack  of  oxygen  causes  a  dissociation 
of  either  «-  or  ,3-colloid  dextrose  derived  from  proteid,  which 
dextrose  then  appears  in  the  urine.  This  suggestion  is,  how- 
ever, highly  speculative. 

One  of  the  very  pronounced  characteristics  of  the  diabetic 
is  his  constant  emaciation.  There  is  always  a  larger  excretion 
of  nitrogen  in  the  urine  than  is  necessary  for  a  healthy  person. 
It  may  be  recalled  that  carbohydrates  diminish  the  proteid 
metabolism,  and  also  that  a  person  may  support  hfe  on  meat  and 
fat  alone  without  tissue  waste.  But  in  this  latter  case  there  is 
a  supply  of  carbohydrate  derived  from  proteid  metabolism. 
This  is  also  true  in  starvation.  But  when  the  proteid  sugar  is 
withdrawn  from  the  tissue  cells  in  diabetes,  there  is  at  once  a 
largely  increased  proteid  metabolism.  This  is  most  obvious  in 
fasting  animals  treated  with  phlorhizin,  as  this  glycosuria  can 
be  immediately  induced.  The  increase  in  proteid  metabolism 
is  most  marked  where  the  higher  D  :  N  ratio  exists.  In  this 
connection  the  following  experiments  on  fasting  animals  are 
suggestive. 

>Straub:  "Archiv  fur  ex.  Path,  und  Pharm.,"  1896,  Bd.  xxxv'iii,  p.  139. 
'Seelig:  Ibid.,  1905,  Bd.  lii,  p.  481. 


METABOLISM    IN    DIABETES. 


235 


TABLE  ILLUSTRATING  THE  INFLUENCE  OF  DIABETES  ON 
PROTEID  METABOLISM. 


Goat.  I 

D0G.2 

D. 

N. 

D:N 

D. 

X. 

D  :N. 

Fasting 

372 

4.04 

Fasting 

3-71 

.... 

4-17 

Fasting  and  diabetic 

20-33 

4.90 

4-15 

63-55 

12.66 

^.02 

" 

26.08 

8.83 

2-95 

65-30 

1S.76 

3-38 

"                      " 

23-39 

8.06 

2.90 

65.84 

18.57 

3-54 

19.01 

6.84 

2.78 

64.60 

17.29 

3-74 

In  the  goat  the  proteid  metaboKsm  rose  to  238,  in  the  dog  to 
450  per  cent,  of  that  in  the  normal  animals,  as  the  result  of  the 
falling  away  of  the  influence  of  the  small  quantity  of  proteid 
sugar  produced  in  starvation. 

In  the  case  of  diabetes  melhtus  reported  by  Mandel  and 
Lusk,  where  the  ratio  D  :  X  was  3.65  :  i  it  was  found  that  the 
ingestion  of  broths  containing  7.7  grams  of  nitrogen  was  fol- 
lowed by  an  ehmination  of  21.7  grams  of  nitrogen  in  the  urine 
or  a  loss  of  body  nitrogen  approximating  14  grams.  The  patient 
was  greatly  emaciated,  and  passed  this  day  in  bed.  He  could 
not  be  maintained  in  nitrogen  equihbrium  with  19  grams  of 
proteid  nitrogen  in  the  food,  but  was  in  nitrogen  equihbrium 
when  given  27  grams.  In  all  cases  of  intense  diabetes  this  fac- 
tor of  an  increased  proteid  metaboKsm  must  be  considered. 
In  mild  cases  in  which  sugar  disappears  from  the  urine  when 
carbohydrates  are  cut  out  of  the  food,  and  in  which  the  patient 
may  burn  his  proteid  sugar,  the  proteid  metabolism  is  not 
different  from  that  of  a  normal  person  living  on  meat  and 
fat. 

Among  the  earliest  work  of  Pettenkofer  and  Voit^  was  a 
respiration  experiment  on  a  diabetic  individual.     The  authors 

'  Lusk:  "Zeitschrift  fiir  Biologie,"  1901,  Bd.  xlii,  p.  43. 
^  Reilly,  Nolan,  and  Lusk:  ".\merican  Journal  of  Physiolog}',"  1895,  vol.  i, 
P-   397- 

^Pettenkofer  and  Voit:  "Zeitschrift  fiir  Biologie,"  1867,  Bd.  iii,  p.  380. 


236  SCIENCE   OF   NUTRITION. 

compared  the  metabolism  of  a  diabetic  with  that  of  a  normal 
man,  as  is  indicated  in  the  following  table: 

COMPARISON  OF  A  NORMAL  AND  A  DIABETIC  MAN. 

Grams  Grams  Burned 

IN  THE  Food.  in  the  Body. 

Healthy  man,  Protcid 120  120 

"     '       "      Fat 112  83 

"      Sugar 344  344 

Diabetic  man,  Proteid 107  158 

"      Fat 108  158 

"      Sugar 337  o 

(  337  grams  of  sugar  in  the  urine.) 

It  is  seen  here  that  the  fat  and  proteid  metabohsm  are  in- 
creased in  order  to  compensate  for  the  non-combustion  of  the 
sugar.  Several  years  later,  on  the  basis  of  these  experiments, 
E.  Voit  calculated  that  a  diabetic  on  a  moderate  mixed  diet 
yielded  1015  calories  per  square  meter  of  surface  while  the 
normal  individual  of  similar  build  produced  1020  calories. 

The  diabetic  condition  therefore,  does  not  involve  a  decrease 
in  the  quantity  of  energy  produced,  but  only  an  alteration  in  the 
source  of  the  energy.  This  fact  can  be  made  still  more  strik- 
ingly apparent  by  comparing  the  metabolism  of  a  normal  fasting 
dog  with  the  metabolism  of  the  same  dog  made  diabetic  with 
phlorhizin.  Such  an  experiment  was  first  done  by  the  writer^  on 
a  fasting  dog  of  1 1  kilograms  and  with  the  following  results: 

COMPARISON    OF    NORMAL    AND    DIABETIC  METABOLISM  IN 
THE  SAME  FASTING  DOG. 

Grams  Burned  Calories  from 

IN  THE  Body.  Met.^bolism. 

Normal,  Proteid 20.19  80.68 

Fat 55.87  526.13 

Total 606.81 

Diabetic,  Proteid 67.38  128.08 

Fat 51.15  481.69 

Total 605.77 

(39.4  grams  de.xtrose  in  urine.     D  :N  ::  3.65  :  i) 

It  is  apparent  from  the  above  experiment  that  the  proteid 
metabohsm  of  the  diabetic  dog  increased  to  333  per  cent,  of  that 

'  Lusk:  "Zeitschrift  ftir  Biologic,"  1901,  Bd.  xlii,  p.  31. 


METABOLISM   IN   DIABETES.  237 

of  the  dog  when  normal.  The  fat  metabolism  slightly  decreased, 
but  the  total  energy  derived  from  the  metaboHsm  was  exactly 
the  same  in  both  cases. 

Rubner  ^  has  rightly  criticised  this  experiment  for  neglect  to 
record  the  temperature  at  which  it  was  carried  out.  Rubner 
has  repeated  the  work  when  the  dog  was  kept  in  a  room  having 
the  temperature  of  ;^7,°,  but  the  D  :  N  ratio  in  this  dog  was  only 
2.8  :  I  on  the  second  day  of  diabetes,  and  Rubner  also  did  not 
take  into  account  the  prehminary  clearing  out  of  the  body 
sugar  which  raised  his  ratio  on  the  first  day.  These  facts,  how- 
ever, do  not  invalidate  his  conclusions. 

Rubner  finds  the  metabolism  on  the  fasting  days  to  be  the 
equivalent  of  477.8  calories  and  on  the  diabetic  days  to  be  510.4, 
an  increase  of  32.3  calories  per  day  in  diabetes.  This  increase 
Rubner  attributes  to  the  specific  d}Tiamic  action  of  the  increased 
proteid  metaboHsm.  This  increase  in  proteid  destruction  in  the 
diabetic  dog  amounted  to  the  equivalent  of  loi.i  calories. 
Rubner  therefore  calculates  that  through  the  extra  metaboHsm 
of  the  equivalent  of  100  calories  in  proteid,  31.9  of  extra  heat 
production  arises.  This  agrees  with  his  values  elsewhere  dis- 
cussed (p.  137).  Rubner's  results  do  not  conflict  with  the 
writer's  experiment,  for  at  a  room  temperature  below  t,t,°  the 
calories  of  the  chemical  regulation  of  temperature  are  replaceable 
by  those  derived  from  the  specific  dynamic  action  of  proteid, 
without  any  alteration  in  the  total  of  the  metabolism. 

The  specific  dynamic  action  of  proteid  ingested  in  diabetes 
is  also  illustrated  in  the  experiment  given  on  page  233.  The 
knowledge  at  hand  makes  it  possible  to  estimate  the  energy 
value  of  proteid  to  the  diabetic.  It  may  be  calculated  from  the 
D  :  N  :  :  3.65  :  i  that  52.5  per  cent,  of  the  energy  in  meat  pro- 
teid is  lost  to  the  organism  in  the  form  of  dextrose.  Rubner 
teaches  that  28.5  per  cent,  of  the  energy  of  meat  proteid  is  never 
utilized  in  the  service  of  the  life  processes  of  the  cell,  but  is 
Uberated  as  free  heat  (p.  140).  There  remains  a  balance  of  only 
19  per  cent,  which  is  actually  available  for  maintenance  of  the 

*  Rubner:  "Gesetze  des  Energieverbrauchs,"  1902,  p.  370. 


238  SCIENCE   OF   NUTRITION. 

vital  activities  in  diabetes.  The  three  to  fivefold  increase  in 
proteid  metabolism,  however,  nearly  neutralizes  this  great  waste 
of  energy,  and  leaves  the  fat  metabolism  very  much  as  in  the 
normal  organism. 

The  distribution  of  the  energy  from  proteid  in  the  diabetic, 
as  described  above,  may  thus  be  summarized: 

100  Proteid  Calories. 

28.5  for  cleavage  and  denitrogenization.    71.5  for  life  processes. 
Deduct 52.5  energy  in  dextrose. 

iQ.o  balance  available  =  x. 

The  production  of  dextrose  from  proteid  involves  the  ab- 
sorption of  a  good  quantity  of  oxygen.  Magnus-Levy,^  calcu- 
lating that  60  grams  of  dextrose  arise  from  those  decomposition 
products  of  100  grams  of  proteid  which  do  not  appear  in  the 
urine  and  feces  (p.  37),  gives  the  following  table  indicating  the 
requirement  for  oxygen  when  proteid  bums  in  diabetes: 

100  grams  proteid      =  38.6  C.  4.24  H.  9.24  O. 

60      "      dextrose    =  24.0  C.  4.0    H.  32.0     O. 


Balance  requiring 

respiratory  O  ....  +  14.6  C.  -|-  0.24  H.  — 22.8     O. 

A  further  calculation  showed  that  the  respiratory  quotient 
for  proteid  in  this  diabetic  condition  was  reduced  from  the  nor- 
mal of  0.808  to  0.613.  Hence  in  severe  diabetes  the  respiratory 
quotient  may  fall  below  that  representing  fat  metabolism. 

An  accompaniment  of  diabetes  which  is  also  present  in 
fasting  (p.  63)  is  the  occurrence  of  acetone,  acetoacetic  and 
sometimes  /?-oxybutyric  acid  in  the  organism  and  in  the  urine. 
These  substances  occur  in  the  absence  of  dextrose  metabolism, 
and  are  believed  by  Geelmuyden-  to  owe  their  origin  to  fat 
metabolism.  The  quantity  of  these  substances  has  been  held  to 
be  a  valuable  aid  in  prognosis.^ 

'  Magnus-Levy:  "Archiv  fiir  Physiologie,"  1904,  p.  379. 

'  Geelmuyden:  "Zeitschrift  fiir  Physiologische  Chemie,"  1897,  Bd.  xxiii, 
p.  431- 

'  Herter  and  Wakeman:  "New  York  University  Bulletin  of  the  Medical 
Sciences,"  1901,  vol.  i,  p.  8. 


METABOLISM   IN    DIABETES.  239 

However,  von  Noorden  ^  reports  cases  of  diabetics  v\^ho  have 
excreted  5-6  grams  of  acetone  and  30-40  grams  of  /3-oxybutyric 
acid  in  a  day,  and  yet  have  hved  comfortably  for  years.  In  the 
patient  of  Mandel  and  Lusk  already  mentioned,  with  a  D  :  N 
ratio  of  3.65  :  i  and  a  complete  intolerance  for  carbohydrates, 
there  was  no  /3-oxybutyric  acid  and  the  acetone  in  the  urine  was 
scarcely  half  a  gram  (0.8  gram  at  a  maximum).  Magnus-Levy  ^ 
has  noted  as  much  as  160  grams  of  /3-oxybutyric  in  the  day's 
urine  of  a  diabetic. 

Magnus-Levy  was  the  first  to  call  attention  to  a  close  relation 
beheved  to  exist  between  the  accumulation  of  /3-oxybutyric  acid 
and  diabetic  coma.  Administration  of  an  alkali  may  delay  but 
does  not  prevent  the  onset  of  diabetic  coma.  Von  Noorden,^ 
from  experiments  of  Herter  and  Wilbur,  concludes  that  the  neu- 
tral salt  of  oxybutyric  acid  is  more  toxic  than  has  been  beheved. 

Schwarz*  notes  that  the  administration  of  butter  and  of 
bacon  to  diabetics  increases  the  acetonuria  and  that  different 
fatty  acids  have  varying  powers  of  so  doing.  He  finds  the  lower 
fatty  acids,  such  as  butyric  acid,  have  the  greatest  effect  in  this 
connection,  and  the  higher  ones,  such  as  oleic  acid,  have  the 
least.  Such  experiments  would  indicate  that  oleomargarin 
with  its  small  content  of  lower  fatty  acids  is  preferable  to  butter 
as  a  food  for  the  diabetic.  Schwarz  determined  the  acetone  in 
the  breath  as  well  as  the  acetone  and  ,5-oxybutyric  acid  in  the 
urine. 

Curiously  enough,  Joslin  ^  has  shown  that  oleic  acid  may 
nearly  double  the  acetonuria  in  a  fasting  man,  while  butyric  acid 
has  no  effect.  JosKn  believes  that  Schwarz's  results  with  higher 
fatty  acids  may  have  been  due  to  the  lack  of  absorption. 

The  whole  question  is  in  an  unsettled  condition. 

'  Von  Noorden:  Von  Leyden's  "Handbuch  der  Ernahrungstherapie,"  1904, 
Bd.  ii,  p.  253. 

*  Magnus-Levy:  "  Archiv fiir ex.  Path.  u.  Pharm.,"  1899,  Bd.  xlii,  p.  232 
'  Von  Noorden:  "Diabetes,"  1905,  p.  99. 

*  Schwarz:  "Deutsches  Archiv  fur  klinische  Medizin,"  1903,  Bd.  Ixxvi,  p. 
243- 

^  Joslin:  "Journal  of  Medical  Research,"  1904,  vol.  xii,  p.  433. 


240  SCIENCE   OF   NUTRITION, 

Minkowski '  noted  that  the  Hvers  of  his  depancreatized  dogs 
were  free  from  glycogen  and  this  fact  has  been  confirmed  by 
other  observers.  He  also  found  that  when  levulose  was  given, 
glycogen  could  be  stored.  The  glycogenic  function  is  inhibited 
in  so  far  as  glycogen  production  from  dextrose  is  concerned,  but 
it  is  not  destroyed  as  regards  levulose  and  galactose.  This 
relation  may  simply  indicate  that,  perhaps  through  some  prop- 
erty of  the  liver,  glycogen  is  not  formed  from  dextrose  when 
dextrose  is  needed  for  the  tissues. 

Von  Noorden^  states  that  the  inabihty  of  the  organism  to 
form  glycogen  is  the  true  cause  of  the  non-combustion  of  sugar 
and  that  sugar  to  be  burned  must  be  polymerized  into  the 
higher  compound.  An  argument  against  this  idea  is  that  when 
the  glycogen  residual  in  the  fasting  organism  diabetic  with 
phlorhizin  is  influenced  by  tetanus,  it  is  not  burned,  but  it  is 
thrown  into  the  blood  and  urine  as  extra  sugar  (p.  71).  This 
experiment  would  indicate  that  the  normal  utiHzation  of  gly- 
cogen by  the  muscle  involves  its  preliminary  conversion  into 
sugar. 

The  present  discussion  of  metabolism  in  diabetes  has  been 
principally  directed  along  hncs  involving  the  most  intense  forms, 
where  the  ability  to  burn  sugar  is  totally  absent.  It  has  been 
observed  that  there  are  many  intermediary  stages  in  this  dis- 
ease in  which  the  power  to  burn  dextrose  is  vastly  different. 
To  determine  the  intensity  of  diabetes.  Von  Noorden  has  pre- 
pared a  standard  test-diet  which  is  largely  employed  in  Ger- 
many. This  diet  is  divided  into  portions  for  three  meals.  At 
breakfast  and  at  lunch  fifty  grams  of  bread  are  allowed.  The 
other  nutrients  are  meat,  eggs,  bacon,  butter,  green  vegetables, 
cheese,  lettuce  salad,  coffee,  and  wine.  Should  the  urine  of 
the  diabetic  be  free  from  sugar  on  such  a  diet,  the  diabetes  is 
mild  in  character.  More  bread  may  then  be  added  to  the  diet 
from  time  to  time  and  the  commencement  of  sugar  excretion  in 
the  urine  watched.     When  sugar  appears  the  limit  of  tolerance 

'  Minkowski:  Loc.  cit. 

^  Von  Noorden:  "Diabetes,"  1905,  p.  57. 


METABOLISM  IN  DIABETES.  241 

for  carbohydrate  has  been  reached.  If,  however,  the  urine 
contains  sugar  on  the  above  test-diet,  the  quantity  of  bread  is 
reduced,  and  the  urine  may  then  become  free  from  sugar. 
If  the  urine  contains  sugar  after  all  the  bread  has  been  removed 
from  the  diet,  the  case  is  one  of  severe  diabetes.  Even  here  the 
sugar  may  disappear  from  the  urine  on  reducing  the  proteid  in 
the  diet  and  thereby  cutting  down  one  supply  of  carbohydrate. 
A  diabetic  of  this  order  may  live  on  a  low  proteid  dietary  with 
enough  fat  to  furnish  suihcient  energy  for  his  body's  require- 
ment, even  as  a  normal  man  may  exist. 

Mandel  and  Lusk^  have  commended  another  method  for  the 
clinical  examination  of  severe  types  of  diabetes,  using  the  D  :  N 
ratio  for  this  purpose.  The  procedure  is  as  follows:  If  a  dia- 
betic be  given  a  meat-fat  diet  (rich  cream,  meat,  butter,  and 
eggs)  and  the  twenty-four  hour  urine  of  the  second  day  be 
properly  collected,"  the  discovery  of  3.65  grams  of  dextrose  to 
one  gram  of  nitrogen  signifies  a  complete  intolerance  for  carbo- 
hydrates and  probably  a  quickly  fatal  outcome.  The  authors 
called  this  (D  :N  "3.65  :  i)  the  fatal  ratio. 

A  lower  ratio  of  dextrose  to  nitrogen  on  this  diet  indicates 
that  some  proteid  sugar  may  be  burned.  Such  a  tolerance  for 
sugar  may  be  increased  on  a  meat-fat  diet  so  that  the  D  :  N 
ratio  falls,  and  in  favorable  cases  the  dextrose  may  entirely 
disappear  from  the  urine. 

In  the  case  of  the  medical  student  of  Mandel  and  Lusk,  the 
ratio  was  constantly  3.65  :  i  and  the  progress  of  the  disease 
rapidly  fatal,  death  occurring  six  weeks  after  the  ratio  was  dis- 
covered. In  another  case  of  the  same  investigators,  a  diabetic 
was  revived  from  coma  with  sodium  bicarbonate;  then,  after 
two  days,  the  meat-fat  diet  was  given.  On  the  second  day  of 
this  diet  the  D  :  N  ratio  was  2.91  :i;  on  the  tenth  day,  0.34:1; 

*  Mandel  and  Lusk:  "Deutsches  Archiv  fiir  klinische  Medizin,"  1904, 
Bd.  Ixxxi,  p.  472. 

^  The  urine  should  be  collected  so  that  an  eariy  morning  hour  (before  break- 
fast) terminates  the  period  for  one  day.  This  is  necessary  because  the  dex- 
trose arising  from  ingested  proteid  is  ehminated  before  the  nitrogen  belonging 
to  the  same  (p.  in).  The  long  period  between  the  evening  meal  and  break- 
fast allows  for  the  ehmination  of  both  constituents. 
16 


242  SCIENCE   OF  NUTRITION. 

on  the  twenty-third  day  the  patient's  urine  was  free  from  sugar 
and  he  was  eating  a  small  amount  of  carbohydrate.  This  is  an 
illustration  of  improving  tolerance  when  a  diabetic  is  placed  on 
a  diet  which  is  free  from  carbohydrates.  Good  practice  calls 
for  the  occasional  interpolation  of  periods  in  which  the  dietary 
is  free  from  carbohydrates,  on  account  of  the  beneficent  effect 
on  the  power  of  the  diabetic  to  burn  sugar. 

The  above-mentioned  individual  now  appears  to  be  doing 
well,  two  years  after  the  test,  but  must  look  carefully  to  his 
dietary.  His  D  :  N  ratio  after  one  week  of  a  strict  meat  and 
fat  diet  is  2.8  :  i,  which  indicates  a  less  favorable  outlook  than 
two  years  ago.     He  has  not  lost  in  weight. 

Physicians  will  object  to  this  manner  of  investigation  be- 
cause there  is  no  ready  method  of  determining  the  nitrogen  in 
the  urine.  With  the  growth  of  laboratories  for  medical  work, 
this  difficulty  will  be  removed.  A  frequent  source  of  error  is 
the  untrustworthiness  of  the  ordinary  diabetic  patient,  who 
will  privately  eat  carbohydrate  in  spite  of  the  physician's  pro- 
hibition. 

Having  discovered  by  investigation  the  tolerance  of  a  dia- 
betic for  carbohydrates,  the  next  step  is  to  see  that  the  patient 
is  supplied  with  a  sufficient  amount  of  energy  in  the  food  to 
correspond  with  the  requirement  of  his  organism  (35  calories 
per  kilogram).  A  diabetic  with  no  tolerance  for  carbohydrates 
will  require  between  200  and  250  grams  of  fat  according  to  his 
weight.  This  amount  will  not  be  taken  unless  all  the  devices  of 
variation  in  flavor  be  made  use  of.  The  patient  will  not  take  it 
of  his  own  accord,  and  the  amount  required  should  be  carefully 
allotted,  preferably  in  a  sanatorium.  Diabetics  can  be  educated 
in  such  establishments  to  a  proper  course  of  dieting  which  is  the 
only  hope  for  the  amelioration  of  their  troubles.  Alcohol  may 
be  used,  in  part,  to  furnish  the  necessary  calories  in  the  diet. 

There  is  no  known  cure  for  diabetes.  There  is  nothing 
except  dieting  that  affords  permanent  relief.  Opium  is  said  to 
reduce  the  sugar  output  in  cases  bordering  oh  the  severe  type.^ 

'Von  Noorden:  "Diabetes,"  1905,  p.   158. 


METABOLISM   IN   DIABETES.  243 

The  cause  of  this  action  is  unknown.  Experiments  inaugurated 
upon  an  individual  having  the  3.65  :  i  ratio  might  indicate 
whether  its  effect  was  really  to  increase  the  combustion  of  sugar 
or  only  to  reduce  the  general  metaboHsm.  The  ingestion  of  ex- 
tracts of  different  organs  does  not  apparently  influence  the  sugar 
excretion.  Laboratory  investigations  of  the  glycolytic  power  of 
pancreas  extracts  have  been  very  numerous,  but  have  failed  to 
give  striking  results.  It  is  possible  that  the  supposed  enzyme 
is  extremely  sensitive  to  a  change  in  normal  conditions.  Mandel 
and  Lusk  gave  large  quantities  of  yeast  to  a  diabetic  man  with- 
out changing  the  D :  N  ;:  3.65  :  i,  which  shows  that  the  enzymes 
of  yeast  are  not  able  to  permeate  the  intestinal  wall  so  that  they 
may  replace  the  natural  ferment  of  the  organism. 

Minkowski  discovered  that  levulose  largely  reduced  proteid 
metabolism  in  the  case  of  depancreatized  dogs.  This  led  to  the 
widespread  use  of  levulose  in  diabetes.  Mandel  and  Lusk, 
however,  found  that  the  increase  of  sugar  in  the  urine  of  their 
diabetic  man,  after  giving  100  grams  of  levulose,  was  80  per 
cent,  of  the  sugar  ingested.  The  levulose  had  no  effect  what- 
ever on  proteid  metabolism. 

Von  Noorden^  confirms  this  observation.  He  also  states 
that  in  severe  cases  of  diabetes,  levulose  appears  in  the  urine. 
He  beheves  that  levulose  is  normally  produced  in  metabohsm 
and  is  normally  burned.  In  very  rare  cases  called  levulosuria, 
levulose  alone  appears  in  the  urine.  One  case  of  complete 
intolerance  for  levulose  has  been  reported.^  Very  likely  in  Min- 
kowski's depancreatized  dogs  the  combustion  power  for  levulose 
was  entirely  normal. 

The  negative  results  as  regards  the  value  of  levulose  were 
especially  interesting  in  the  case  of  Mandel  and  Lusk.  This 
diabetic  medical  student  was  confident  of  the  efficacy  of  levu- 
lose on  account  of  opinions  expressed  by  the  writer  in  his  lectures. 
On  the  days  of  levulose  ingestion  the  patient's  spirits  revived, 

'  Minkowski:  hoc.  cit.,  p.  131. 
^  VonNoorden:  Loc.  cit.,  p.  50. 
^Neubauer:  "Miinchenermed.  Wochenschrift,"  1905,  p.  1523. 


244  SCIENCE   OF   NUTRITION. 

his  strength,  measured  on  the  ergograph,  decidedly  improved 
and  his  companions  remarked  upon  the  benefit  received.  All 
of  which  shows  that  subjective  sensations  are  not  to  be  used  as 
scientific  criteria. 

In  this  connection  it  may  be  mentioned  that  (/-glucuronic  acid 
and  pentoses  have  a  bearing  on  carbohydrate  metabolism.  A 
large  variety  of  substances  (camphor,  chloral,  turpentine)  form 
syntheses  with  glucuronic  acid  in  the  organism,  and  correspond- 
ing glucuronates  are  then  eHminated  in  the  urine.  At  first 
glance  glucuronic  acid  appears  to  be  the  preliminary  oxidation 
product  of  glucose,  as  is  suggested  by  the   following  equation: 

OHC  (CH0H),CH20H  +  Oj  =  OHC  (CHOH),COOH  +  HjO 
Dextrose.  Glucuronic  acid. 

However,  Mandel  and  Jackson^  administered  camphor  to 
fasting  dogs  for  several  days  and  noted  the  excretion  of  glucu- 
ronic acid.  On  giving  large  quantities  of  dextrose  the  proteid 
metabohsm  fell  and  with  it  the  glucuronic  acid  elimination;  and 
on  giving  the  animal  chopped  meat  the  quantity  of  campho- 
glucuronic  acid  in  the  urine  was  correspondingly  increased.  It 
may  be  safely  inferred  that  glucuronic  acid  is  produced  solely 
in  the  intermediary  metabolism  of  proteid.  For  the  large  liter- 
ature on  this  subject,  and  also  on  the  pentoses,  the  reader  is 
referred  to  other  sources.' 

Pentoses,  which  are  sugars  containing  five  atoms  of  carbon, 
have  been  detected  in  animal  and  vegetable  tissue.  Hammar- 
sten  found  a  pentose  in  the  nucleoproteid  of  the  pancreas. 
Neuberg  showed  that  this  pentose  and  the  one  obtained  from 
nucleoproteid  in  the  liver  is  /-xylose.  Grund^  has  found  pen- 
toses in  all  the  organs  of  the  body,  particularly  in  those  rich 
in  nuclear  material. 

Salkowski  and  Neuberg  have  shown  that  /-xylose  may  be 
derived  through  ferment  action  on  (/-glucuronic  acid.     Salkow- 

'  Mandel  and  Jackson:  "American  Journal  of  Phvsiolog}',"  1902,  vol.  viii. 
Proceedings  of  the  American  Physiological  Society,  p.  xiii. 

'  Neuberg:  "Ergebnisse  der  Physiologic  "  iqo4,  Bd.  iii,  i  Abtheilung,  p.  373. 
'  Grund:  "Zeitschrift  fiir  physiologische  Chemie,"  1902,  Bd.  xxxv,  p.  iii. 


METABOLISM   IN  DIABETES. 


245 


ski  was  the  first  to  detect  a  pentose  in  the  urine,  and  this  Neu- 
berg  has  shown  to  be  i-arabinose.  The  ehmination  of  pentoses 
in  the  urine  may  accompany  diabetes,  but  in  extremely  rare 
cases  a  simple  pentosuria  occurs  in  which  pentose  is  the  only 
sugar  appearing  in  the  urine. 

Luzzatto^  reports  such  a  case  in  which  the  elimination  of 
arabinose  was  independent  of  diet  or  mental  or  muscular  effort. 
Luzzatto  believes  the  pentose  in  this  case  to  have  been  /-arab- 
inose. Neuberg  finds  that  in  the  normal  rabbit  /-arabinose  is 
more  readily  burned  than  (^-arabinose.  Luzzatto's  case  could 
be  explained  by  supposing  that  the  body  had  lost  its  normal 
power  to  burn  /-arabinose  as  normally  produced  in  metabolism. 

Pentosuria  is  occasionally  discovered  in  the  routine  of  life 
insurance  examinations.  So  far  as  known  it  is  without  danger 
to  general  health. 

Cremer,^  in  a  series  of  excellent  experiments,  has  shown  that 
a  vegetable  pentose,  such  as  rhamnose,  may  be  burned  in  a 
rabbit  and  spare  an  isodynamic  equivalent  of  fat.  In  one  rabbit, 
on  a  fasting  day,  the  total  metabolism  amounted  to  129.1  cal- 
ories (proteid,  22.5  and  fat,  106.6),  and  on  the  day  when  rhamnose 
was  given  to  128.4  calories  (proteid,  21.36;  fat,  32.9,  and  rham- 
nose 74.11). 

Lindemann  and  May^  found  that  90  grams  of  rhamnose 
could  be  used  by  a  normal  man.  When,  however,  rhamnose  was 
given  to  a  diabetic  individual  whose  urine  had  been  sugar  free, 
sugar  appeared  in  the  urine.  In  cases  of  severe  diabetes  re- 
ported by  von  Jacksch  *  it  was  found  that  rhamnose,  arabinose 
and  xylose  tended  to  increase  the  proteid  metabolism,  and  hence 
the  sugar  output,  and  also  brought  about  diarrhea.  The  use 
of  pentoses  in  diabetes  has  therefore  not  been  successful. 

Opie^  has  endeavored  to  estabhsh  a  connection  between 

*  Luzzatto:  "Hofmeister's  Beitrage,"   1904,  Bd.  vi,  p.  87. 

'  Cremer:  "Zeitschrift  fiir  Biologic,"  1901,  Bd.  xlii,  p.  428. 

'  Lindemann  and  May:  "Deutsches  Archiv  fiir  klin.  Med.,"  1896,  Bd.  Ivi, 
p.  282. 

^  Von  Jacksch:  Ibid.,  1899,  Bd.  Ixiii,  p.  612. 

^  Opie:  "Journal  of  Experimental  Medicine,"  1901,  vol.  v,  p.  397. 


246  SCIENCE   OF   NUTRITION. 

changes  in  the  islands  of  Langerhans  of  the  pancreas  and  the 
cause  of  diabetes.  Janeway  and  Oertel/  von  Noorden,  and 
others,  have  reported  autopsies  on  cases  of  severe  diabetes  in 
which  the  pancreas  appeared  perfectly  normal.  It  is  not  always 
possible  to  observe  with  the  microscope  the  cause  of  patho- 
logical change  in  function. 

On  autopsy  in  diabetes  large  quantities  of  fat  are  found  in 
the  liver  and  muscles.  The  same  is  observed  in  chloroform 
narcosis  when  sugar  appears  in  the  urine,  in  anemia,  and  after 
respiration  of  rarefied  air,  where  lactic  acid  is  eliminated  in  the 
urine  (p.  215),  and  in  phosphorus-  and  arsenic-poisoning,  which 
are  similarly  accompanied  by  an  elimination  of  lactic  acid. 
These  phenomena  are  always  associated  with  an  increased  pro- 
teid  metabolism.  Fat  likewise  appears  in  the  mammary  glands 
during  lactation  (p.  201). 

Virchow  assumed  a  fatty  degeneration  of  proteid  in  which 
the  tissue  proteid  was  converted  into  fat,  as  distinguished  from 
a  fatty  infiltration  in  which  body  fat  passed  into  the  cells. 
Much  of  the  earlier  writing  of  Voit  is  pervaded  with  the  idea  of 
a  considerable  origin  of  fat  from  proteid  (p.  120).  The  idea  of 
a  fatty  degeneration  of  proteid  in  the  old  sense  has  been  largely 
overturned  by  the  work  of  Rosenfeld.^  Rosenfeld  finds  that  if 
a  dog  be  starved  and  then  given  sheep's  fat,  and  again  starved, 
the  ingested  fat  will  be  found  deposited  as  sheep's  fat  in  his 
adipose  tissue,  while  the  liver  will  contain  about  10  per  cent,  of 
fat,  and  this  characteristic  dog  fat.  If  now  phosphorus-  or 
phlorhizin-poisoning  be  induced  and  the  Hver  be  examined,  40 
per  cent,  of  fat  may  be  found  therein  and  this  in  the  form  of 
sheep's  fat.  Hence,  in  these  cases  the  fat  is  simply  transported 
to  the  liver  from  the  fat  deposits  of  the  body.  The  fat  in  the 
blood  is  largely  increased.^  The  fat  becomes  normal  in  quan- 
tity in  the  liver  twenty- four  hours  after  the  cessation  of  the  phlor- 
hizin  action.     It  is  retransported  to  the  depots  of  fat  deposit. 

*  Janeway  and  Oertel:  "  Virchow's  Archiv,"  1903,  Bd.  cLxxi,  p.  547. 
'  Rosenfeld:  "Ergebnisse  der  Physiologic,"  1903,  Bd.  ii,  I,  p.  50. 
^  B.  Fischer  ("Virchow's  Archiv,"  1903,  Bd.  clxxii,  pp.  30,  218)    reports  a 
case  of  coma  diabeticum  in  which  the  blood  serum  contained  23  per  cent,  of  fat. 


METABOLISM   IN   PHOSPHORUS-POISONING.  247 

If  a  fatty  "degeneration"  were  to  be  found  anywhere,  it 
would  certainly  be  looked  for  in  the  dying  cells  of  the  phos- 
phorus liver,  or  in  the  analogous  condition  of  acute  yellow 
atrophy  of  the  liver.     But  another  explanation  avails. 

Mandel^  has  shown  that  lactic  acid  disappears  from  the 
blood  and  urine  of  a  phosphorized  dog  if  phlorhizin  glycosuria 
be  induced.  The  writer  believes  that  the  lactic  acid  which 
occurs  is  derived  from  the  sugar  formed  in  proteid  metabolism. 
In  the  above  case  the  sugar  is  removed  before  its  conversion  into 
lactic  acid.  In  phlorhizin  diabetes,  dextrose  does  not  bum; 
in  phosphorus-poisoning  lactic  acid  derived  from  dextrose 
does  not  burn.  In  both  cases  a  sugar-hungry  cell,  or  one 
where  carbohydrate  is  not  oxidized,  is  found,  and  under  these 
circumstances  fat  is  attracted  to  the  cell,  and  in  larger  quan- 
tities than  can  be  useful.  Wherever  sugar  freely  burns  this  fatty 
infiltration  is  impossible  (p.  143).  A  reduced  local  circulation 
in  a  portion  of  the  heart  may  produce  anemia  of  the  part,  an 
imperfect  local  combustion  of  lactic  acid  normally  formed, 
and  a  fatty  infiltration  of  the  locahty.  The  writer  offers  this 
general  hypothesis  as  his  explanation  of  fatty  changes  in  tissue 
in  general. 

It  has  been  stated  that  the  action  of  phosphorus  is  to 
induce  autolysis  (self-digestion)  of  the  body's  protoplasm 
(Jacoby,^  WaldvogeP),  since  leucin,  tyrosin,  and  other  amino 
acids  may  be  eliminated  in  considerable  quantity  in  the  urine. 
Oswald*  thinks  that  phosphorus  destroys  or  weakens  the  antiau- 
tolytic  agents  of  the  body.  That  autolytic  enzymes  do  not  gain 
free  control  over  the  cells  through  the  direct  influence  of  phos- 
phorus, is  proved  by  the  work  of  Ray,  McDermott,  and  Lusk.^ 
These  authors  found  that  phosphorus  injections  raised  the  pro- 
teid metabolism  of  fasting  dogs  to  250,  260,  283,  248,  183,  and 

^  Mandel:  "American  Journal  of  Physiology,"  1905,  vol.  xiii,  p.  xvi. 
^  Jacoby:  "Zeitschrift  fiir  physiologische  Chemie,"  1900,  Bd.  xxx,  p.  174. 
^  Waldvogel:  "Archiv  fiir  klinische  Medizin,"  1905,  Bd.  Ixxxii,  p.  437. 
■*  Oswald:  " Biochemisches  Centralblatt,"  1905,  Bd.  iii,  p.  365. 
^  Ray,  McDermott,  and  Lusk:  "American  Journal  of  Physiology,"  1899, 
vol.  iii,  p.  139. 


248  SCIENCE    OF    NUTRITION. 

164  per  cent,  of  that  of  the  clog  ^vhen  normal.  They  contrasted 
this  increased  proteid  metabolism  with  that  obtained  in  phlor- 
hizin  glycosuria,  which  is  represented  by  increases  to  540,  450, 
340,  and  340  per  cent.  When,  however,  they  gave  phlorhizin 
and  obtained  the  increased  metaboHsm,  and  then  injected  phos- 
phorus, this  was  not  followed  by  any  marked  increase  in  proteid 
metabolism.  Under  these  circumstances  phlorhizin  glycosuria 
is  the  predominating  factor,  removing  the  dextrose  produced 
from  proteid.  As  regards  phosphorus-poisoning  Araki'  be- 
lieves that  lactic  acid  accumulation  is  due  to  lack  of  oxygenation 
of  the  tissues  caused  by  a  slow  heart-beat,  but  not  due  to 
anemia.  He  does  not  believe  the  oxygen  deprivation  to  be 
very  pronounced.  The  writer  offers  the  explanation  that  phos- 
phorus may  affect  the  enzyme  which  breaks  up  the  lactic  acid 
derived  from  dextrose,  and  the  accumulation  of  this  acid  may 
prevent  the  action  of  some  of  the  denitrogenizing  enzymes;  and 
further,  its  non-combustion  may  necessitate  an  increase  of  pro- 
teid metabolism. 

This  theory  is  strengthened  by  the  discovery  of  Schryver^ 
that  the  addition  of  lactic  acid  favors  the  accumulation  of 
amino  acids  in  autolysis  of  the  hver. 

Claude  Bernard  showed  that  dextrose,  whether  derived  from 
proteid  or  starch,  was  convertible  into  glycogen,  and  this  again 
was  changeable  back  into  dextrose.  Present  knowledge  adds 
lactic  acid  to  both  ends  of  this  chain  in  showing  the  following 
possible  progression  of  events, — lactic  acid,  dextrose,  glycogen, 
dextrose,  lactic  acid. 

Quite  pertinent  to  this  theoretical  discussion  is  the  obser- 
vation of  von  Jacksch^  on  a  patient  who  recovered  from  phos- 
phorus-poisoning, and  in  whom  a  desire  for  carbohydrates 
marked  the  beginning  of  convalescence. 

'  Araki:    "Zeitschrift  fiir  physiologische  Chemie,"  1892,  Bd.  xvii,  p.  337. 
'Schryver:  "The  Bio-Chemical  Journal,"  1906,  vol.  i,  p.  153. 
^  Von   Jacksch:    "Zeitschrift   fur   physiologische   Chemie,"   1903,  Bd.  xl, 
p.  123. 


CHAPTER  XIII. 
METABOLISM  IN  FEVER. 

By  fever  is  generally  understood  a  complex  of  phenomena 
whose  dominant  characteristic  is  a  rise  of  body  temperature. 
If  the  term  fever  be  confined  simply  to  the  latter  aspect,  one 
might  classify  fevers  as  follows: 

(i)  Physiological  fever,  induced,  for  example,  by  immersion 
in  a  hot  bath  at  a  temperature  of  40°,  which  prevents  the  normal 
loss  of  body  heat  through  radiation  and  conduction.  (2)  Neu- 
rogenic fever,  as  brought  about  by  the  direct  stimulation  of  nerve- 
cells  in  the  corpora  striata  of  the  mid-brain.  (3)  Aseptic  fever, 
due  to  the  resolution  of  blood- cells  or  crushed  tissue  in  the 
organism.  (4)  Infective  fever,  produced  after  the  infection  of 
the  organism  by  certain  bacteria  or  their  products  and  by  some 
protozoa.  Or,  one  may  consider  fever  as  being  due  to  infection 
by  bacteria  or  protozoa,  and  include  all  other  increases  of  tem- 
perature under  the  term  of  hyperthermia. 

In  a  previous  chapter  the- mechanism  of  normal  heat  regu- 
lation has  been  explained.  It  was  there  noted  that  on  a  warm, 
moist  day  the  temperature  of  a  fat  individual,  when  he  was 
working  hard,  rose  considerably  above  the  normal.  This  effect, 
if  carried  to  an  extreme,  results  in  sunstroke,  where  the  over- 
heating of  the  body  causes  a  rapid  pulse,  accompanied  by  dizzi- 
ness, delirium,  or  unconsciousness.  But  in  the  great  majority 
of  cases  the  body  temperature  remains  delicately  balanced, 
notwithstanding  changes  in  outside  environment,  or  internal 
heat  production.  In  the  fat  person  at  hard  work  the  condition 
of  increased  metabolism  is  combined  with  that  of  difficult  dis- 
charge of  heat.  A  person  placed  in  a  bath  at  40°  would  be  sub- 
ject to  conditions  where  there  could  be  no  heat  loss  but  rather 
a  gain  in  heat,  even  though  his  metabolism  were  low.     In  a 

249 


250  SCIENCE   OF   NUTRITION. 

normal  person,  therefore,  a  rise  in  temperature  may  be  due  to 
increased  heat  production,  with  difficulty  in  discharging  it,  or 
a  check  of  heat  loss  may  be  the  only  factor  of  the  higher  tem- 
perature. In  the  discussion  of  fever  one  is  confronted  by  two 
possible  factors:  (i)  an  increase  in  heat  production,  and 
(2)  a  decrease  in  the  facilities  for  the  discharge  of  heat  produced. 

It  has  already  been  set  forth  that  the  metabolism  in  a  cold- 
blooded animal  increases  with  the  temperature  of  his  environ- 
ment. Warmed  tissue  metabolizes  more  material  than  cooled 
tissue.  It  is  therefore  to  be  expected  that  the  metabolism  in  an 
organism  which  has  been  warmed  to  fever  heat  will  be  greater 
than  the  normal.  This  was  beautifully  shown  in  the  experi- 
ments of  Pfiuger,^  who  subjected  both  curarized  and  normal 
rabbits  to  external  warmth  which  raised  their  temperatures. 
In  the  animals  whose  voluntary  muscles  were  paralyzed  by 
curare,  as  the  rectal  temperature  rose  from  39°  to  41°,  the  oxy- 
gen absorption  increased  10  per  cent,  for  each  degree  of  tem- 
perature increase.  In  the  normal  animals  the  increased  me- 
tabolism between  temperatures  of  38.6°  and  40.6°  was  shown 
by  increases  of  5.7  per  cent,  for  oxygen,  and  6.8  per  cent,  for 
carbon  dioxid  for  a  rise  of  one  degree  of  temperature. 

It  has  been  noted  in  another  chapter  (p.  93)  that  Rubner 
found  in  man  that  a  bath  at  a  temperature  of  35°  had  no  effect 
on  metabolism,  while  one  at  44°  increased  the  volume  of  respira- 
tion 18.8  per  cent.,  the  oxygen  absorption  17.3  per  cent.,  and 
the  carbon  dioxid  ehmination  32.1  per  cent.  Linser  and  Schmid^ 
confirm  these  results  in  experiments  on  two  men  suffering  from 
ichthyosis  hystrix,  which  involved  almost  complete  loss  of  func- 
tion of  the  sweat  glands.  The  body  temperature  of  these  men 
could  be  varied  by  altering  the  temperature  of  their  living  room 
between  30°  and  38°.  The  humidity  of  the  room  was  from 
40  to  50  per  cent.  The  maximum  increase  in  the  metabolism 
of  these  individuals  is  represented  by  a  rise  in  carbon  dioxid 

'  Pfliiger:  "Pfliiger's  Archiv,"  1878,  Bd.  xviii,  pp.  303,  356. 
*  Linser  and  Schmid:  "Archiv  fiir  klinische  Medizin,"    1904,   Bd.   Ixxix, 
P-  514- 


METABOLISM   IN    FEVER.  25 1 

excretion  from  3.8  c.c.  per  minute  and  kilogram  at  the  body 
temperature  of  36.2°  to  5.3  c.c.  per  minute  and  kilogram  at  39°. 
The  number  of  respirations,  which  were  from  12  to  15  per  minute 
at  36°,  increased  to  20  and  22  at  39°.  The  total  increase  in  the 
carbon  dioxid  output,  due  to  a  rise  of  3°  through  simple  warming 
of  cells,  amounted  to  40  per  cent. 

The  next  question  is  of  the  nature  of  the  materials  which  are 
oxidized.  It  has  long  been  known  that  urea  excretion  is  abnor- 
mally high  in  fever,  and  this  led  to  the  inquiry  whether  the  cause 
was  merely  the  result  of  increased  body  temperature  or  due  to 
toxic  influences.  Thus,  Schleich^  finds  that  a  man  in  nitrogen 
equilibrium  is  affected  by  an  hour's  bath  in  water  between  40.5° 
and  41.5°  which  causes  his  temperature  to  reach  39.7°,  so  that  his 
nitrogen  metabolism  for  the  day  increases  18,  22,  and  37  per  cent. 
Other  authors  have  not  found  any  increase,  but  Linser  and 
Schmid^  explain  these  divergences  of  opinion  by  showing  that 
an  increase  of  body  temperature  to  39°  in  man  has  no  effect  on 
proteid  metaboUsm,  but  that  above  this  there  is  always  an  in- 
creased destruction  of  proteid.  They  therefore  conclude  that  in 
toxic  fevers  where  the  temperature  is  not  above  39°  any  increase 
of  proteid  metabolism  must  be  due  to  the  toxic  processes  and  not 
to  the  hyperthermia. 

F.  Voit^  found  that  on  artificially  raising  the  temperature  of 
a  fasting  dog  to  40°  or  41°  for  a  period  of  twelve  hours,  there  was 
an  increase  in  nitrogen  elimination  of  37  per  cent,  above  the 
normal.  Warming  for  a  period  of  only  three  hours  had 
slight  effect.  If,  however,  the  animal  were  fed  with  meat  and 
fat,  warming  increased  the  proteid  metabolism  only  4  per  cent. 
If  the  animal  were  given  30  to  40  grams  of  cane  sugar,  no 
increased  metaboHsm  of  proteid  followed  the  rise  in  temper- 
ature to  41°.  It  is  apparent  that  the  ingestion  of  proteid  and 
carbohydrates  may  control  this  rise  in  proteid  destruction  due 

'  Schleich:  "Archiv  fiir  ex.  Path,  und  Pharm.,"  1S75,  Bd.  iv,  p.  90. 
^  Linser  and  Schmid:  Loc.  cit. 

^  Voit,  F. :  "  Sitzungsberichte  der  Gesellschaf t  fiir  Morphologie  und  Phys- 
iologie,"  1895,  Heft  ii,  p.  120. 


252  SCIENCE   OF  NUTRITION. 

to  a  febrile  temperature.  F.  Voit  explains  the  increase  in  pro- 
teid  metabolism  in  hyperthermia  as  due  to  the  quick  combustion 
of  glycogen  and  the  consequent  impoverishment  of  the  tissues 
as  regards  carbohydrate  material.  Proteid  or  carbohydrate 
ingested  furnish  the  necessary  carbohydrate  and  prevent  the 
hyperthermal  rise  in  proteid  metabolism.  The  destruction  of 
proteid  due  to  toxic  processes  cannot  be  so  easily  controlled,  as 
will  be  seen  later. 

If  certain  portions  of  the  brain  be  punctured,  and  particu- 
larly the  region  of  the  corpora  striata,  a  high  fever  sets  in.  Here 
again  there  is  an  increased  output  of  carbon  dioxid  and  a  rise 
in  proteid  metabohsm.  This  phenomenon  has  been  recently 
investigated  by  Hirsch,  Miiller,  and  Roily \  and  by  Roily-  alone. 
They  fmd  that  after  the  "heat  puncture"  of  the  corpora  striata 
the  Hver,  blood  and  skin  become  warmer  than  the  muscles, 
although  normally  the  muscles  are  warmer  than  the  skin. 
They  find  that  the  heat  puncture  is  effective  even  in  curarized 
animals,  where  the  muscles  are  free  from  nerve  stimuH.  Roily 
finds,  however,  that  the  heat  puncture  is  unsuccessful  if  the 
liver  of  the  rabbit  has  been  previously  freed  from  glycogen  by 
strychnin  convulsions.  Under  these  circumstances  there  is  no 
rise  in  temperature  nor  concomitant  rise  in  proteid  metabohsm. 
The  inference  is  that  the  fever  in  question  is  due  to  nerxQ  im- 
pulses which  increase  the  metabohsm  of  carbohydrate  in  the  liver. 
In  infectious  fever  there  is  little  glycogen  in  the  organism,  but 
that  the  fever  in  this  case  is  due  to  other  causes  than  the  rapid 
combustion  of  carbohydrates  was  shown  by  Roily,  who  infected 
a  rabbit,  which  had  been  freed  from  glycogen  as  above  described, 
with  a  culture  of  pneumococci  and  obtained  as  great  a  rise  in 
temperature  and  proteid  metabolism  as  would  have  occurred 
had  the  tissues  of  the  rabbit  been  rich  in  carbohydrates.  The 
rise  in  temperature  after  puncture  of  the  corpora  striata  may  be 
termed  neurogenic  fever,  and  it  is  like  its  companion,  the  gly- 
cosuria following  Claude  Bernard's  puncture,  in  that  its  mechan- 

'  Hirsch,  Muller,  and  Roily:  "Deutsches  Archiv  fur  klin.Med.,"  1903,  Bd. 
Ixxv,  p.  264.  '  Roily:  Ibid.,  1903,  Bd.  Ixxviii,  p.  250. 


METABOLISM   IN    FEVER. 


253 


ism  is  no  more  invoked  in  true  infectious  fever  than  are  the  nerve 
centers  in  diabetes  mellitus  (p.  226). 

If  the  extent  of  metabolism  in  infectious  fevers  be  inves- 
tigated and  compared  with  that  found  in  simple  hyperthermia, 
a  very  analogous  state  of  affairs  is  discovered.  The  course 
taken  by  the  metabolism  in  toxic  fevers  is,  as  a  rule,  (i)  a  slight 
rise  in  proteid  metabolism,  even  before  the  fever  sets  in;  (2) 
increased  metabohsm  with  heat  retention  and  increased  proteid 
destruction;  (3)  heat  production  and  heat  outgo  become  equal, 
with  the  body  at  a  higher  temperature  level.  These  factors  are 
illustrated  in  the  experiments  of  May^  on  fasting  rabbits  in- 
jected with  a  culture  of  erysipelas  of  the  pig.  The  results  of 
these  respiration  experiments  with  three  rabbits,  in  which  the 
normal,  transition,  and  fever  periods  were  investigated,  are 
given  below. 


METABOLISM  IN  FEVER  IN  RABBITS    (May). 


H 


Day 
OF  Fast. 


Body 

Temperature. 


39-2-39-5 
39.7-41.2 
41.2-40.7 

38-5-38.2 
38.2-38.6 
38.6-38.6 
38.7-40.1 

39.0-39.6 
39.6-39.2 
39.7-41.0 


Calories. 


61.9 
63-9 
73-3 

53-8 
54-0 
55-4 
61.2 

64-5 
64.2 
65.8 


From 
Pro- 
teid. 


19 
27 

16.8 
18.5 
20.6 
27.9 


From 
Fat. 


44 
45 
46 

37 
35-6 
34-8 
33-3 


10.7  53.8 

ro.4  I  53-7 

1 1.8  I  54.0 


Remarks. 


Normal. 

Injection. 

Fever. 

Normal. 

Injection. 
•  Fever. 

Normal. 

Injection. 


The  above  table  shows  a  slight  increase  in  the  proteid  me- 
tabohsm on  the  day  of  infection.  It  also  shows  that  a  high 
fever  may  be  reached  by  the  end  of  the  twenty-four  hours  after 
the  injection  without  materially  altering  the  heat  production 
of  the  day.     It  demonstrates  that  on  the  day  of  continued  fever 

'  May:  "Zeitschrift  fiir  Biologic,"  1894,  Bd.  xxx,  p.  i. 


254  SCIENCE   OF   NUTRITION. 

the  metabolism  increases,  and  this  at  the  expense  of  an  increased 
destruction  of  proteid,  while  the  fat  consumption  remains  un- 
ahered.  A  calculation  shows  that  on  the  days  of  high  fever 
20  per  cent,  more  energy  was  produced  in  rabbit  E,  and  15  per 
cent,  more  in  rabbit  G,  than  on  normal  days.  Since  Traube's 
writings  on  the  subject,  the  cause  of  fever  has  been  attributed, 
not  to  great  heat  production,  but  to  a  disturbance  in  the  mech- 
anism for  the  regulation  of  heat  loss.  On  recalhng  the  fact 
that  the  metabolism  of  a  fasting  dog  may  be  raised  from  100 
calories  in  starvation  to  189  calories  after  giving  meat  (p.  129), 
without  any  change  of  body  temperature,  it  becomes  evident 
that  the  rise  in  metabolism  in  fever  is  too  insignificant  to  be  the 
cause  of  the  rise  in  temperature.  In  fact,  as  has  been  already 
set  forth,  the  rise  in  body  temperature  from  failure  of  the  phys- 
ical regulation  may  of  itself  explain  the  increase  in  heat  pro- 
duction. Thus  a  calculation  made  in  the  case  of  rabbit  E 
shows  that  the  carbon  dioxid  elimination  is  increased  6.6  per 
cent,  for  each  degree  of  rise  in  temperature,  which  corresponds 
to  Pfliiger's  experiments,  before  mentioned,  in  which  artifi- 
cially warmed  normal  rabbits  excreted  6.8  per  cent,  more  carbon 
dioxid  for  each  degree  of  rise  in  temperature. 

Long  before  May's  experiments,  Wood^  had  found  an 
average  increase  of  23  per  cent,  (calculated  by  Welch)  in  the 
heat  production  of  fasting  dogs  after  inducing  fever;  and  he  also 
found  that  mere  ingestion  of  food  by  a  normal  dog  would 
cause  a  greater  heat  production  than  fever  itself. 

Traube  attributed  the  cause  of  fever  to  a  cramp-like  con- 
striction of  the  peripheral  arterioles  which  prevented  the  proper 
distribution  of  blood  at  the  surface,  and  therefore  hindered  the 
normal  cooling  of  the  body. 

The  effect  of  a  cold  bath  upon  a  vigorous  man  is  to  constrict 
the  peripheral  blood-vessels  and  to  increase  the  heat  production. 
The  body  temperature,  instead  of  falling,  may  rise  for  eight  or 
ten  minutes  and  then  sink.^     If  the  individual  pass  from  the  bath 

'Wood:  "Fever,"  Philadelphia,  iSSo. 

^  Lefevre,  J.:  " Comptes  rendus  soc.  biol.,"  1894,  T.  46,  p.  604. 


METABOLISM  IN   FEVER.  255 

during  the  earlier  minutes  the  hot  blood  comes  to  the  surface 
to  be  cooled,  and  the  body  glows  with  a  red  color,  the  so-called 
"reaction."  This  experiment  shows  that  there  are  factors 
invoked  during  the  first  few  minutes  which  prevent  the  dis- 
charge of  the  heat  produced.  One  factor  must  be  a  general 
constriction  of  the  peripheral  arteries,  causing  the  blood  to 
remain  in  the  heat  producing  inner  organs  of  the  body.  In 
this  experiment,  therefore,  cooling  of  the  organism  is  prevented 
by  the  mechanism  of  physical  regulation  above  described,  and 
the  mechanism  of  chemical  regulation  which  reflexly  increases 
heat  production. 

To  combat  a  rise  in  temperature,  however,  the  only  means 
available  is  the  physical  regulation, — i.  e.,  the  distribution  of  the 
blood  and  the  production  of  sweat.  If  these  avenues  of  heat 
loss  be  diminished  or  shut  off,  heat  accumulates  within  the  body 
and  temperature  rises.  How  an  increase  in  heat  production 
of  89  per  cent,  may  not  cause  a  rise  in  temperature  in  a  normal 
animal  has  already  been  described;  whereas,  a  high  fever  may 
be  accompanied  by  an  increased  metabolism  of  only  15  per  cent. 
The  cause  of  the  fever  must  therefore  be  due  to  diminution  in 
the  ability  to  discharge  the  heat  produced. 

In  further  support  of  this.  Senator  has  shown  that  the  fever 
following  pus  injections  in  a  dog  begins  with  a  retention  of  heat 
within  his  body.  Nebelthau  ^  found  that  when  the  heat  discharge 
of  a  normal  rabbit  was  called  100,  during  the  first  twelve  hours 
of  infection  in  which  the  temperature  rose  from  38.6°  to  40.1°, 
the  discharge  of  heat  was  but  96.3.  Assuming  the  heat  produc- 
tion to  ha.ve  been  the  same  in  these  two  periods  (as  was  actu- 
ally the  case  in  the  rabbits  of  May)  then  the  heat  retained  would 
account  for  the  pathological  increase  in  temperature.  At  a 
later  stage  the  discharge  of  heat  rose  to  equalize  its  production 
at  the  higher  temperature. 

Nebelthau  has  shown  a  fall  in  temperature  and  heat  produc- 
tion in  a  rabbit  whose  cord  was  divided  between  the  sixth  and 
seventh  cervical  vertebrjae,  and  has  also  demonstrated  that  under 

^  Nebelthau:  "Zeitschrift  fiir  Biologic,"  1S95,  Bd.  xxxi,  p.  353. 


256  SCIENCE   OF  NUTRITION. 

these  circumstances  infection  with  erysipelas  of  the  pig  had  no 
influence  on  temperature  or  heat  production.  The  inference  is 
that  the  febrile  toxins  act  through  the  higher  vasomotcr  centers, 
whose  regulatory  control  is  lost  in  the  above  experiment. 

A  kindred  interpretation  may  be  placed  on  the  experiments 
of  Mendelson,*  who  was  unable  to  produce  fever  through  pus 
injections  when  the  dog  was  under  the  influence  of  chloral  or 
morphin,  although  such  treatment  in  a  normal  animal  caused 
a  rise  in  temperature  of  from  36.3°  to  39.9°  in  forty-five  minutes. 
Mendelson  also  finds  a  constant  constriction  of  the  renal  blood- 
vessels in  fever. 

Further  experimentation  convinced  Sawadowsky-  that  fever 
could  not  be  produced  after  the  mid-brain  was  severed  from  the 
medulla,  whereas  if  the  mid-brain  be  left  intact  but  the  cere- 
brum be  sectioned  from  it,  fever  may  be  induced  in  the  ordinary 
course.  The  toxic  substance  must  therefore  act  on  nerve- cells 
in  the  mid-brain,  which  in  turn  stimulate  the  medullary  centers. 

At  times  during  high  fever  the  skin  may  be  red  and  the  periph- 
eral blood-vessels  distended.  Although  there  is  no  sufficient 
explanation  for  this,  Krehl^  suggests  that  the  quantity  of  blood 
flowing  through  the  vessels  at  the  time  may  be  inadequate  to 
reduce  the  body's  temperature. 

The  second  means  of  physical  regulation  of  the  body  tem- 
perature is  through  the  evaporation  of  water  both  from  the  lungs 
and  the  sweat  glands.  It  might  be  surmised  that  the  activity  of 
this  mechanism  was  reduced  in  fever.  Nebelthau*  has  shown 
that  the  heat  lost  by  evaporation  of  water,  and  by  radiation  and 
conduction,  bore  exactly  the  same  ratio  to  each  other  in  normal 
and  in  fever-infected  rabbits.  Since  Rubner  (p.  90)  has  proved 
that  the  elimination  of  water  in  normal  animals  greatly  increases 
at  high  temperatures,  the  mere  maintenance  of  the  usual  water 
evaporation  during  fever  would  of  itself  be  abnormal. 

^  Mendelson:  "Virchow's  Archiv,"  1885,  Bd.  c,  p.  274. 
'Sawadowsky:  "  Centralblatt  fiir  medizinische  Wissenschaft,"  1888. 
^  Krehl:  "  Pathologische  Physiologic,"  1904,  p.  453. 
*  Nebelthau:  Loc.  cit. 


METABOLISM   IN    FEVER.  257 

No  complete  metabolism  experiment  on  a  man  suffering 
from  high  fever  has  ever  been  made,  and  here  is  an  opportunity 
for  some  one  to  perform  a  rare  service.  By  no  means  the  least 
interesting  phase  of  such  an  experiment  would  be  the  course  of 
water  elimination  from  the  skin. 

Lang^  has  sho\ATi  that  the  elimination  of  sweat  is  reduced 
during  the  rise  of  temperature  in  man,  but  at  the  height  of  fever 
is  the  same  as  the  normal,  while  there  is  some  increased  evapo- 
ration from  the  lungs. 

Recent  experiments  by  Schwenkenbecker  and  Inagaki^ 
show  that  the  "insensible  perspiration"  in  fever  is  as  great  as 
in  health,  and  that  although  the  urine  may  decrease  in  quantity 
there  is  no  actual  accumulation  of  water  in  the  body  as  was  be- 
lieved by  von  Leyden. 

Lang^  has  also  shown  that  the  secretion  of  sweat  is  increased 
50  per  cent,  after  the  ingestion  of  food  as  against  an  increase 
of  70  per  cent,  in  the  normal  individual. 

In  intermittent  fever  profuse  perspiration  is  certainly  an 
important  factor  in  the  reduction  of  temperature  at  the  end  of 
the  febrile  stage. 

It  may  be  concluded,  as  Krehl  emphatically  states,  that 
insufficiency  of  water  evaporation  plays  a  not  unimportant  role 
in  the  febrile  rise  in  temperature.  The  body  might  be  cooled 
were  the  sweat  glands  freely  active. 

The  production  of  heat  in  fever  may  be  greatly  increased 
during  a  chill,  and  a  rapid  rise  in  temperature  may  follow. 
This  was  shown  by  Liebermeister^  in  a  case  of  malaria.  The 
temperature  rose  from  36.9°  in  the  first  half  hour  to  39.5°  at  the 
end  of  another  hour,  while  the  carbon  dioxid  expired  rose  from 
13.85  grams  to  34.20  grams  per  half  hour.  This  was  a  case  of 
chill  with  shivering.     This  increased  metabolism  is  due  to  the 

'  Lang:  "  Archiv  fiir  klinische  Medizin,"  1903,  Bd.  Ixxix,  p.  343. 

^  Schwenkenbecker  and  Inagaki:  "Archiv  fiir  ex.  Path,  und  Pharm.,"  1906, 
Bd.  liv,  p.  168. 

^  Lang:  Loc.  cit. 

*  Liebermeister:  "Deutsches  Archiv  fur  klinisches  Medizin,"  1871,  Bd. 
viii,  p.  153. 

17 


258  SCIENCE   OF   NUTRITION. 

mechanism  of  chemical  regulation.  The  blood  is  driven  from 
the  skin  by  vaso-constriction,  those  end-organs  of  the  skin  which 
are  sensitive  to  cold  are  strongly  stimulated,  with  the  result  that 
there  is  a  reflex  increase  of  heat  production.  That  this  is  true 
is  shown  by  the  fact  that  if  the  cold  stimulation  be  removed  by 
supplying  a  warm  environment,  the  attending  phenomena  pass 
off  (Krehl.)^ 

Any  muscular  exercise,  such  as  sitting  up,  increases  metab- 
olism, and  may  under  some  circumstances  cause  a  rise  in  temper- 
ature in  fever.  The  diurnal  variation  of  temperature  is  similar 
in  character  to  that  of  health,  but  its  fluctuations  are  much  more 
extreme,  on  account  of  the  increased  excitabihty  of  the  vaso- 
motor control  of  the  discharge  of  heat.  The  parallelism  be- 
tween the  amount  of  the  metabohsm  and  the  height  of  the  tem- 
perature during  the  day  is  shown  in  Fig.  9,  taken  from 
Riethus.^ 

It  is  apparent  that  cold  and  muscular  work  increase  metab- 
olism and  temperature  in  fever,  and  it  may  be  also  surmised 
that  large  proteid  ingestion,  which  by  its  specific  dynamic 
action  increases  heat  production,  will  likewise  increase  the 
body's  temperature  at  a  time  when  heat  discharge  is  difficult 
(p.  140). 

May'  summarizes  the  conditions  of  metabohsm  in  fever  in 
the  following  statement:  "There  is  an  increased  proteid  metab- 
olism but  no  increased  fat  metabohsm,  except  such  as  may 
incidentally  result  from  dyspnea,  chill,  or  muscular  activity." 

Infectious  fevers  are  characterized  by  a  toxic  destruction  of 
body  proteid.  Sometimes,  as  in  the  earlier  stages  of  tuber- 
culosis, this  tissue  destruction  may  be  present  in  the  absence  of 
fever  itself.  Such  a  toxic  action  on  body  proteid  is  also  ob- 
served in  cancerous  cases,  as  was  described  by  Fr.  jMiiller.* 
Miiller  writes:  "In  the  seven  cases  (of  carcinoma)  cited,  the 

'  Krehl:  " Pathologische  Physiologic,"  1904,  p.  452. 

*  Riethus:  "Archiv  fur  ex.  Path,  und  Pharm.,"  1900,  Bd.  xliv,  p.  239. 
'  May:  Ott's  "Chemische  Pathologic  dcr  Tuberculose,"  1903,  p.  355. 

*  MuUcr,  F.:  "Zeitschrift  fiir  klinische  Medizin,"  1889,  Bd.  xvi,  p.  496. 


METABOLISM   EST   FEVER. 


259 


Fig.  9. — Case  of  abdominal  typhoid  (Riethus).  The  figures  i  to  6  on  the 
left  represent  the  amount  in  c.c.  of  COj  and  O,  of  respiration  per  kilogram  and 
minute.  The  measurements  were  all  made  during  fasting.  The  Oj  curve  may 
be  considered  as  nearly  proportional  to  the  heat  production  (p.  32). 


26o  SCIENCE   OF   NUTRITION. 

nitrogen  excretion  was  larger  than  the  nitrogen  ingestion  and 
consequently  the  body  lost  proteid.  In  two  cases  the  proteid 
loss  was  no  greater  than  in  healthy  individuals  with  similar 
insufficient  nourishment.  In  all  the  other  cases  the  proteid 
metabolism  was  decidedly  above  that  of  healthy  men  under  the 
same  conditions.  Even  an  ample  dietary  was  not  able  to  estab- 
lish nitrogen  equilibrium.  As  more  food  was  given  the  nitrogen 
ehmination  rose  higher  and  higher,  but  the  point  of  nitrogen 
.  equihbrium  seemed  unattainable."  Miiller  compared  the 
cachexia  of  carcinoma  with  that  found  in  febrile  processes  and 
believed  them  to  be  analogous. 

As  regards  tuberculosis  Alay  ^  writes:  "Larger  quantities  of 
the  toxins  produce,  with  certain  exceptions,  a  direct  injury  to 
the  cell  protoplasm.  They  are  strongly  toxic.  The  quantity 
of  proteid  destruction  attributable  to  this  cause  is  not  very  large 
and  becomes  of  importance  only  when  continued  for  a  long  period 
of  time  and  where  there  is  no  compensatory  regeneration.  It 
appears  that  the  power  to  regenerate  on  the  part  of  these  cells 
which  are  destroyed  by  toxins  is  greatly  reduced  and  in  severe 
cases  entirely  lost." 

Other  fevers  show  a  high  toxic  destruction  of  proteid.  F. 
Miiller-  reports  a  daily  loss  of  10.8  grams  of  nitrogen  (equal  to 
318  grams  of  muscle)  by  a  typhoid  patient  during  eight  days  of 
fever.  During  fever  in  croupous  pneumonia,  the  proteid  metab- 
oHsm  is  much  higher  than  normal.  After  the  crisis  there  is  still 
a  large  excretion  of  nitrogen  in  the  urine  which  continues  until 
the  croupous  exudate  has  been  decomposed  by  autolysis,  ab- 
sorbed by  the  blood,  and  metabolized  in  the  body  (epicritical 
nitrogen  elimination).  In  acute  pneumonic  phthisis  (galloping 
consumption),  with  its  caseous  transformation  of  lung  tissue, 
there  is  a  very  high  waste  of  tissue  proteid.  F.  Miiller^  has 
shown  that  while  the  croupous  exudate  readily  undergoes  auto- 

'  May:  Ott's  "  Chemische  Pathologic  der  Tuberculose,"  1903,  p.  335. 
'  Miiller,  F.:  "  Ccntralblatt  fiir  klinische  Medizin,"  1884,  No.  xxxvi. 
'Miiller,   F. :   " Verhandlungen  des  20   Congresses  fiir  innere  Medizin," 
1902,  p,  192. 


METABOLISM   IN   FEVER.  261 

lysis  at  a  temperature  of  40°,  with  the  production  of  deutero- 
albumoses,  lysin,  leucin,  tyrosin,  etc.,  the  caseous  mass  does 
not  undergo  autolysis  although  it  permits  free  diffusion  of  solu- 
ble material,  such  as  phosphates.  Hence,  although  the  proteid 
of  the  cheesy  mass  is  insoluble  in  the  organism,  the  soluble 
toxins  may  be  absorbed  from  the  diseased  part,  and  be  the 
causative  agent  of  the  rapid  destruction  of  body  proteid  in  gal- 
loping consumption. 

The  above  analysis  of  metabolism  in  fever  shows  that  the 
small  increase  in  total  metabolism  is  associated  with  increases 
in  proteid  metabohsm  due  (i)  to  the  high  temperature,  and  (2) 
to  the  virulence  with  which  toxins  attack  the  body  tissue.  It 
has  been  shown  that  carbohydrate  ingestion  may  reduce  the 
proteid  destruction  due  to  the  overheating,  and  that  toxic  de- 
struction may  or  may  not  be  compensated  for  by  regenerative 
processes.  Upon  this  general  knowledge  it  is  possible  to  con- 
struct a  dietary  schedule  for  the  patient. 

In  all  fevers  the  septic  products  act  upon  the  hunger  centers 
in  the  brain,  and  appetite  is  wanting.  This  is  evidenced 
throughout  the  course  of  tuberculosis,  for  example,  and  tends  in 
this  case  to  weaken  the  body's  resistance  through  undernutri- 
tion.    Forced  feeding  is  therefore  resorted  to. 

The  experiments  of  von  Hosslin^  strongly  affirmed  the  be- 
neficence of  a  liberal  diet  in  ordinary  fevers.  He  writes: 
"The  results  show  that  febrile  patients,  or  at  least  those  who 
do  not  run  temperatures,  above  40°  to  40.5°,  can  digest  and 
absorb  the  total  amount  of  proteid,  fat  and  carbohydrates 
which  can  be  given  them  with  their  diminished  appetite,  pro- 
vided the  food  is  administered  in  a  proper  form.  Temperature 
and  metabolism  are  only  slightly  increased  thereby." 

A  milk  diet  is  the  usual  course  prescribed  in  fevers.  Since 
milk  is  the  proper  diet  for  a  rapidly  growing  calf,  its  proteid  con- 
tent is  extremely  high.  The  relative  quantity  of  this  ingredient 
may  be  reduced  by  modifying  the  milk  through  the  addition 
of  milk  sugar  or  cream.     In  this  way  von  Leyden  and  Klem- 

*  Von  Hosslin:  "Virchow's  Archiv,"  1882,  Bd.  Ixxxix,  p.  317. 


262  SCIENCE  OF  NUTRITION. 

perer*  have  added  5  per  cent.,  then  7.5,  and  finally  10  per  cent, 
of  milk  sugar  to  whole  milk.  The  last  named  quantity  raises 
the  calorific  value  by  410  calories  per  liter,  and  makes  a  milk 
containing  1050  calories  per  hter.  Two  hters  of  such  milk 
would  be  nearly  or  quite  sufficient  to  cover  the  requirement  of 
an  individual  confined  to  his  bed.  A  milk  so  prepared  may  be 
given  to  most  patients  without  producing  diarrhea  or  indigestion. 
The  taste  is  perfectly  agreeable  to  the  patient.  In  this  way 
carbohydrates  which  are  highly  desirable  in  the  febrile  condition 
can  be  properly  administered.  Von  Leyden  and  Klemperer 
have  also  found  that  an  addition  of  cream  to  milk,  so  that  its 
value  is  increased  by  2.5  per  cent,  of  fat,  or  225  calories  per 
liter,  is  favorably  received  by  the  patient.  Such  a  milk  diet  may 
be  fortified  by  the  addition  of  brandy,  whiskey,  or  sherry.  This 
increases  the  calorific  value  of  the  milk,  but  more  particularly 
gives  it  taste,  and  both  through  the  awakening  of  the  sense  of 
appetite  and  through  direct  action  upon  the  neuro-secretory 
apparatus  of  the  digestive  tract,  favorably  influences  the 
digestion  of  the  food. 

It  seems  strange  that  in  this  country  where  so  much  attention 
has  been  paid  to  the  modification  of  infant  food,  the  preparation 
of  suitable  diet  in  fever  should  have  received  such  scant  attention. 
It  may  well  be  that  investigation  will  show  that  dilution  of 
milk  and  its  fortification  by  ingredients  other  than  proteid 
may  be  as  advantageously  practised  in  fever  cases  as  in  in- 
fant nutrition. 

The  discussion  now  turns  from  these  theoretical  considera- 
tions to  the  actual  results  of  nutritive  investigations  in  fever  as 
presented  by  von  Leyden  and  Klemperer. 

The  following  table  represents  a  case  of  a  typhoid  fever 
patient  to  whom  milk  fortified  with  meat  powder  was  given, 
thereby  producing  a  high  proteid  diet.  The  quantity  of  the 
individual  nutrients,  the  calorific  value  of  the  diet,  and  the 
nitrogen  in  the  urine  and  feces  were  determined.     The  daily 

*  Von  Leyden  and  Klemperer:  Von  Leyden's  "Handbuch  der  Ernahrungs- 
therapie,"  1904,  Bd.  ii,  p.  345. 


METABOLISM  IN   FEVER. 


263 


loss  of  body  nitrogen  was  calculated.     The  results   were  as 
follows : 


METABOLISM  IN  ABDOMINAL 
TYPHOID. 


DIET  HIGH  IN 
PROTEID. 


Food. 

Excreta. 

6  w 

Loss 

High- 
est 
Temp. 

Amount 
IN  Grams. 

Calo- 
ries. 

N. 

Fat. 

a  < 

3: 

Urine 
N. 

Feces 

N. 

Total 

N. 

OF 

Body 

N. 

39-6 

600  milk. 

408 

3-2 

21 

27 

15-76 

0.42 

16.18 

12.98 

39-8 

1000  milk. 

680 

^.^6 

35 

45 

18.96 

0.42 

19-38 

14.02 

40.2 

goo  milk, 

20  meat-powder. 

686 

7.67 

31 

40 

17.88 

0.42 

18.30 

10.63 

39-7 

1200  milk, 
50  meat-powder. 

1002 

13.61 

42 

54 

21.56 

1-75 

23-31 

9.70 

39-9 

1500  milk, 

100  meat-powder. 

1392 

22.45 

52 

67 

28.7 

1-75 

30.45 

8.00 

40.3 

1200  milk, 
50  meat-powder. 

1 188 

20.86 

42 

54 

27.9 

1-75 

29.65 

8.79 

40.3 

1500  milk, 
50  meat-powder. 

1206 

15-2 

52 

67 

21.7 

1.92 

23.62 

8.42 

39-S 

2000  milk, 
50  meat-powder. 

1546 

17.85 

70 

90 

22.9 

1.92 

24.82 

6.97 

40.2 

2000  milk, 

100  meat-powder. 

1732 

25-1 

70 

90 

29.6 

1.92 

31-52 

39-9 

2000  milk, 
50  meat-powder. 

1546 

17-85 

70 

90 

20.85 

2.13 

22.98 

5-13 

39-8 

1200  milk, 

50  meat-powder. 

1002 

13.61 

42 

54 

19.76 

2.13 

21.89 

8.28 

39-9 

1500  milk. 

1020 

8.0 

52 

67 

15-86 

2.13 

18.02 

10.02 

It  will  be  noted  that  there  was  a  large  loss  of  body  nitrogen 
on  every  day  of  the  experiment.  Even  when  the  diet  con- 
tained 25.1  grams  of  nitrogen,  the  excreta  of  the  day  contained 
31.5  grams,  indicating  a  loss  of  6.4  grams  from  the  body.  The 
days  of  the  smallest  loss  of  tissue  nitrogen  were  those  on  which 
the  largest  quantity  (90  grams)  of  carbohydrates  was  given. 
Also  a  diet  containing  17.85  grams  of  nitrogen  seems  to  protect 
the  proteid  waste  about  as  well  as  one  with  25.1  grams  of  nitrogen, 
when  both  diets  contain  equal  quantities  of  carbohydrates 
and  fat. 

Von  Leyden  and  Klemperer  regard  the  above  experiment 
as  indicating  the  advantage  of  a  large  proteid  ingestion  in  pre- 
venting tissue  waste.  But  deficient  calorific  value  and  lack  of 
carbohydrates  may  be  accountable  for  the  increased   w^aste 


264 


SCIENCE   OF   NUTRITION. 


on  the  lower  proteid  diets.  It  must  also  be  remembered  that 
proteid  itself  yields  carbohydrate  in  metaboHsm.  That  carbo- 
hydrates of  themselves  cannot  prevent  the  toxic  waste  of  proteid 
tissue  is  beautifully  illustrated  in  another  experiment  given  by 
the  same  authors.  The  case  was  again  one  of  typhoid,  and 
carbohydrates  were  given  in  large  quantity: 


METABOLISM  IN  ABDOMINAL 
TYPHOID. 


DIET  HIGH  IN 
CARBOHYDR.JiTE. 


Food. 

Excreta. 

Loss 

High- 
est 
Temp. 

Quantity  in  Grams. 

Calo- 
ries. 

XiN 

Grams. 

Fat  in 
Grams. 

Carb. 

IN 

Grams. 

Urine 

N    IN 

Grams. 

Feces 

N    IN 

Grams 

OF 

Body 

N     IN 

Grams. 

39-8 

3808  milk, 
400  lactose, 
60  glucose, 
i  liter  sherry. 

3020 

14.9 

98 

386 

20.1 

1-5 

6.7 

39-7 

2768  milk, 
200  lactose, 
133  glucose, 
i  liter  sherry. 

3295 

14.6 

96 

457 

19.7 

1-5 

6.6 

38.8 

2460  milk, 
300  lactose, 
i  liter  sherry. 

2952 

13-0 

86 

411 

237 

1-3 

12.0 

40.2 

2366  milk, 
300  lactose, 
i  liter  sherry. 

2892 

12-5 

83 

406 

233 

1.2 

12.0 

39-6 

2430  milk. 
109  lactose, 
)  liter  sherry. 

2522 

12.8 

85 

310 

237 

1-3 

12.2 

38.8 

2080  milk, 
200  glucose, 
i  liter  sherry. 

2420 

II. I 

80 

303 

21.8 

I.I 

11.8 

39-2 

1870  milk, 
200  glucose, 
i  liter  sherry. 

2141 

9-9 

65 

344 

ig.4 

1.0 

9-5 

In  this  case  it  is  definitely  shown  that  a  moderate  amount  of 
proteid,  combined  with  a  large  quantity  of  fat  and  carbohydrates 
of  large  energy  content,  does  not  in  any  way  prevent  the  con- 
stant waste  of  body  tissue  in  t}^hoid  fever.  Since  it  has  been 
demonstrated  that  carbohydrates  prevent  tissue  destruction  due 
to  hyperthermia,  it  must  be  assumed  that  the  nitrogen  waste  is 
here  due  to  toxic  destruction  of  the  cells.  An  important  question 
and  one  unanswered  is  this :  Would  the  tissue  waste  have  been 
less  had  more  proteid  been  given?    To  this  vitally  significant 


METABOLISM   IN   FEVER. 


265 


question  there  is  to-day  no  answer.  If  the  tissue  waste  on  this 
diet  is  an  inevitable  consequence  of  the  disease  and  is  not  to  be 
prevented  by  increasing  the  proteid  in  the  food,  then  such  proteid 
increase  is  to  be  avoided  on  account  of  its  extra  heat-producing 
power, — its  specific  dynamic  action. 

An  illustration  of  the  course  of  nitrogen  metabohsm  in  a 
different  fever — namely,  pneumonia — may  also  be  taken  from 
von  Leyden  and  Klemperer.     The  details  are  as  follows : 


METABOLISM  IN  PNEUMONIA. 

Food. 

Excreta. 

Temp,  on 

Successive 

H 

,  i 

Days. 

Quantity 

a 

N. 

Fat. 

§5 

Urine 

Feces 

Total 

Loss  OF 

IN  Grams. 

0 

<  Q 

N. 

N. 

N. 

Body 

< 

"£ 

N. 

40.8  (highest). 

2000  milk. 

1360 

10.6 

70 

90 

24.7 

0.9 

25.6 

15-0 

40.9  (highest). 

2000  milk, 
150  cream, 
ICX5  lactose. 

1980 

11.4 

85 

197 

22.8 

0.9 

237 

12.3 

41.2  at  12  M. 

2000  milk. 

1975 

10.6 

70 

240 

21.7 

0.9 

22.6 

12.0 

36.8  at  7  p.  M. 

150  lactose. 

37.3  (highest). 

2000  milk, 
200  cream. 

1612 

11.7 

90 

99 

21.9 

I.I 

23.0 

II-3 

36.S  (highest). 

2000  milk, 
200  cream, 

1752 

137 

100 

99 

18.5 

I.I 

19.6 

5-9 

2  eggs. 

36.8  (highest). 

2000  milk, 
300  cream, 
4  eggs. 

2018 

17-3 

120 

104 

18.7 

I.I 

19.8 

- 

2.5 

In  the  above  case  it  is  again  demonstrated  that  nitrogen 
equilibrium  cannot  be  obtained  during  high  fever,  and  also 
that  the  loss  of  body  nitrogen  does  not  cease  at  the  crisis,  but 
rather  continues  on  account  of  the  epicritical  elimination  of 
nitrogen  derived  from  the  proteid  of  the  croupous  exudate. 
During  the  time  of  this  epicritical  elimination  the  body  appears 
unable  to  add  new  proteid  to  itself.  About  four  days  after  the 
crisis,  true  convalescence  begins  with  the  upbuilding  of  new  pro- 
teid tissue.  (For  further  details  regarding  nutrition  in  fever  the 
reader  is  referred  to  von  Leyden  and  Klemperer's  admirable 
article,  from  w^hich  the  tables  above  have  been  transcribed.) 

On  autopsy  of  patients  who  have  died  of  fevers,  parenchy- 


266  SCIENCE   OF   NUTRITION. 

matous  and  fatty  degeneration  of  the  organs  have  been  found. 
These  changes  have  been  ascribed  to  overheating  of  the  cells. 

Litten^  warmed  guinea-pigs  artificially  and  noted  fatty  but 
no  parenchymatous  degeneration  of  the  tissues.  The  space  in 
which  the  animals  were  kept  was,  however,  insufficiently  ven- 
tilated, and  the  fatty  change  might  have  been  caused  by  dyspnea, 
as  results  in  normal  animals  (p.  215). 

Naunyn  ^  observed  that  rabbits  might  be  artificially  warmed 
for  thirteen  days  so  that  an  average  body  temperature  of  41.5° 
was  maintained  without  any  parenchymatous  or  fatty  degen- 
eration taking  place.  The  animals  were  supplied  with  ample 
food,  water  and  a  sufficient  supply  of  air.  Naunyn  found  that 
the  red  blood-cells  of  rabbits  and  dogs  remained  intact  even  at 
a  body  temperature  of  42°.  Welch ^  noticed  fatty  but  no  paren- 
chymatous change  in  the  tissues  of  rabbits  after  exposure  to  high 
temperature  for  at  least  a  week.  One  rabbit  which  had  been 
subjected  to  high  temperature  for  four  days  was  inoculated 
with  the  bacilli  of  the  swine  plague  and  died  in  thirty-six  hours 
showing  extreme  fatty  changes  in  the  heart  and  other  organs. 

Ziegler^  discovered  degenerative  changes,  both  parenchy- 
matous and  fatty,  on  artificially  warming  rabbits.  The  exper- 
iment was  continued  in  one  case  for  twenty-nine  days.  He 
however  found  a  great  reduction  (30  per  cent,  and  more)  in  the 
quantity  of  hemoglobin  in  his  rabbits.  It  may  well  be  a  question 
whether  the  fatty  change  noticed  in  the  liver  and  muscles  was 
not  due  to  anemia  instead  of  to  the  hyperthermia.  Since  fatty 
infiltration  is  known  to  be  caused  by  dyspnea,  which  frequently 
terminates  life  in  fever,  one  might  investigate  this  subject  to  see 
whether  parenchymatous  change  in  fever  is  not  solely  due  to  the 
toxins,  and  fatty  change  to  the  anaerobic  cleavage  of  materials 
in  the  cells,  which  always  induces  fatty  infiltration  (p.  246). 

As  regards  the  etiology  of  fever,  various  attempts  have  been 

^Litten:  "Virchow's  Archiv,"  1877,  Bd.  Ixx,  p.  10. 

^  Naunyn:  "  Archiv  fiir  ex.  Path,  und  Pharm.,"  1884,  Bd.  xviii,  p.  49. 

^  Welch:  "Medical  News,"  1888,  vol.  lii,  p.  403. 

*  Ziegler:  "Kongress  fiir  innere  Medizin,"  1895,  Bd.  xiii,  p.  345. 


METABOLISM  IN   FEVER. 


267 


made  to  identify  a  single  factor  which  would  cause  the  high 
temperature. 

Krehl  and  Mathes  ^  find  that  human  urine  during  fever  con- 
tains an  increased  quantity  of  albumoses  which  have  been  shown 
to  possess  a  decidedly  toxic  action  when  introduced  into  animals. 
Klemperer^  denies  that  these  albumoses  have  any  toxic  action, 
and  asserts  that  the 
results  were  due  to 
impurities  in  prep- 
aration. In  other 
respects  the  urine 
has  generally  been 
found  to  be  of  nor- 
mal character. 
Thus  Mohr^  finds 
that  the  relation  C 
to  N  in  the  urine  is 
unchanged  from 
the  normal,  which 
indicates  that  there 
is  no  qualitative 
change  in  the  char- 
acter of  the  general 
proteid  metabo- 
lism. 

However,  there 
is  a  very  note- 
worthy record  made  by  A.  R.  Mandel*  that  the  rise  of  tem- 
perature in  aseptic  or  surgical  fevers  is  accompanied  by  a 
large  increase  in  the  purin  bases  in  the  urine  of  patients  fed  with 
milk.  The  temperature  rises  and  falls  with  the  quantity  of 
purin  bases  eliminated.     The  uric  acid  ehmination  is  reduced 

^  Krehl  and  Mathes:  "  Archiv  fiir  klinische  Medizin,"  1895,  Bd.  liv,  p.  501. 
'  Klemperer:  "Naturforscherversammlung,"  1903,  2,  ii,  p.  67. 
^  Mohr:  "Zeitschrift  ftir  klinische  Medizin,"  1904,  Bd.  Hi,  p.  371. 
*  Mandel:  "American  Journal  of  Physiology,"  1904,  vol.  x,  p.  452. 


GRAM 
PURIN  BASES 

0.07 
0.06 
0.05 
0.0^ 


Fig.   10.- 


0.03 


-Resection  of    knee-joint  for  tubercular 
arthritis. 


268 


SCIENCE   OF  NUTRITION. 


,.TEMPK 


(p.  279).     These  relations  are  illustrated  in  Fig.  10, — a  case  of 
resection  of  the  knee-joint  for  tubercular  arthritis. 

That  the  purin  bases  can  be  the  cause  of  the  rise  of  temper- 
ature is  indicated  by  the  experiments  of  Burian  and  Schur^  ^Yho 
found  that  when  nucleoproteid  was  administered  intravenously 
to  a  dog,  a  rise  of  temperature  followed.  Alandel  showed  that  a 
subcutaneous  injection  of  forty  milligrams  of  xanthin  caused 
a  marked  rise  in  the  temperature  of  a  monkey,  and  that  the  ad- 
ministration of  a  strong  decoction  of  60  grams  of  coffee  (con- 
taining trimcthyl-xanthin)  to  a  man  unused  to  coffee  drinking, 
w^as  followed  by  a  febrile  temperature.  This  is  shown  in  Fig.  11. 
Another  research    available   in  this   connection   is  that  of 

von  Jacksch,"  who  noted 
that  the  purin  bodies  in 
the  urine  of  tuberculous 
patients  may  increase 
from  a  normal  equiva- 
lent of  4.4  per  cent,  of  the 
total  nitrogen  excreted, 
to  one  representing  11. 3, 
or  even  17.39  per  cent. 
Also  Benjamin^  reports  a 
case  of  typhoid  whose 
urine  contained  the  large 
quantity  of  o.i  gram  of 
purin  bases  wnth  0.54 
gram  of  uric  acid.  Such 
results  indicate  abnor- 
mal tissue  destruction,  and  Mandel  believes  that  the  purin 
bases  liberated  through  the  toxic  destruction  of  tissue  would 
have  a  considerable  effect  in  producing  the  temperatures 
discovered. 


GRAM 

PURIN  BASES 
0.06 


0.03 


Fig.  II. 


-Case  A.   M.     Given   decoction  of 
60  gms.  coffee. 


>  Burian  and  Schur:  "Pfluger's  Archiv,"  1901,  Bd.  Ixxxvii,  p.  239. 
'Von  Jacksch:  "Zeitschrift  fur  klinische  Medizin,"  1902,  Bd.  xlvii,  p.  i. 
^Benjamin:  "Salkowski's  Festschrift,"  1904,  p.  61. 


METABOLISM  IN   FEVER.  269 

It  would  indeed  be  a  most  striking  fact  if  it  should  be  found 
that  the  cause  of  the  febrile  temperature  lay  in  the  effect  of  purin 
bases  on  the  heat-regulating  apparatus  of  the  mid-brain  acting 
through  the  vasomotor  system.  Antipyretic^s  do  not  lower  body 
temperature  in  the  normal  organism  in  man.  Is  their  action 
merely  to  nullify  the  activity  of  purin  bases  upon  the  nerve 
centers?  Future  research  alone  can  decide  this.  An  unpub- 
lished work  by  Mandel  in  the  writer's  laboratory  seems  to  show 
that  this  is  the  mode  of  action  in  the  case  of  salicylic  acid.  Per- 
haps such  conjectures  are  out  of  place  in  a  book  of  this  sort, 
but  they  simply  emphasize  the  extraordinary  field  which  lies 
open  to  the  investigator  in  clinical  medicine. 


CHAPTER  XIV. 
PURIN  METABOLISM.— GOUT. 

Uric  acid  was  discovered  in  urinary  calculi  by  Scheele  in 
1776,  and  was  found  to  be  present  in  gouty  concretions  by  Wol- 
laston  in  1797.  It  has  since  been  the  subject  of  investigations 
almost  without  number,  and  of  theoretical  speculation  beyond  that 
of  any  other  chemical  substance  described  in  medical  literature. 
The  older  work  concerning  the  excretion  of  uric  acid  is  almost 
valueless  on  account  of  the  inadequacy  of  the  chemical  methods 
of  the  times.  Accurate  determinations  of  uric  acid  date  from  the 
introduction  of  a  new  method  of  analysis  by  Salkowski  in  1882. 

The  newer  researches  are  also  based  on  more  exact  chem- 
ical knowledge  of  the  precursors  of  uric  acid.  Much  valuable 
information  has  been  gathered  as  regards  the  normal  method  of 
production  of  uric  acid,  although  it  will  be  seen  that  on  the 
pathological  side  there  is  httle  beyond  the  conjectural  to  reward 
the  student. 

Emil  Fischer^  grouped  together  uric  acid,  hypoxanthin, 
xanthin,  adenin  and  guanin  as  bodies  whose  varying  structure 
depended  upon  slight  changes  around  the  chemical  nucleus  of  a 
substance  called  purin.  Purin,  according  to  Fischer,  may 
occur  in  the  body,  but  on  account  of  its  ready  decomposability, 
has  not  been  discovered  there. 

The  relations  between  the  purin  bodies  may  be  judged  from 
the  following  formulae : 

Purin CsH.N^ 

Hypoxanthin C5H4N4O 

Xanthin C^H^N^O^ 

Uric   acid CsH.N.O, 

Adenin CsHjN.NHj 

Guanin CsHjN.ONH^ 

*  Fischer:  "Berichte  der  deutschen  chemischen  Gesellschaft,"  1899,  Bd. 
xxxii,  p.  435. 

270 


PURIN   METABOLISM. GOUT. 


271 


Hypoxanthin,  xanthin,  and  uric  acid  are  respectively  mono-, 
di-,  and  tri-oxypurin.  Adenin  is  aminopurin,  and  guanin  is 
aminohypoxanthin.  It  is  evident  that  uric  acid  is  the  most  highly 
oxidized  product  of  the  series,  and  might  readily  arise  from  the 
oxidation  of  hypoxanthin  and  xanthin.  It  is  also  apparent  that 
by  supplanting  the  NHg  group  in  adenin  and  guanin  by  O,  they 
would  be  converted  into  hypoxanthin  and  xanthin  respectively, 
and  that  from  these  substances  uric  acid  might  arise  through 
further  oxidation. 

For  greater  detail  of  the  chemistry  of  purins,  the  reader  is 
referred  to  any  text-book  on  physiological  chemistry.^  The 
four  precursors  of  uric  acid,  hypoxanthin,  xanthin,  adenin,  and 
guanin  are  collectively  called  the  purin  bases.  The  general 
term,  purin  bodies,  includes  uric  acid  also. 

Since  Salomon  discovered,  in  1880,  that  purin  bases  exist 
in  the  nucleins  which  are  present  in  the  nuclei  of  cells,  a  great 
deal  of  work  has  been  done  to  explain  the  chemical  nature  of 
these  nuclear  constituents.  A  summary  of  the  products  which 
can  be  obtained  from  nucleoproteids  is  as  follows: 


Carbohydrate.- 


Pentoses, 

Hexoses, 

Glucothionic  acid,^ 

A  non-reducing  sub- 
stance which  yields 
levulinic  acid. 


Phosphoric  acid 


Bases. 


Adenin, 
Guanin, 
Xanthin, 
Hypoxanthin, 

Thymin, 
Cytosin, 
Uracil, 


Purin  bases. 


1  Pyramidin 
1       bases. 


^Consult  also  Mendel:  "The  Formation  of  Uric  Acid,"  Harvey  Society 
Lecture,  "Journal  of  the  American  Medical  Association,"  1906,  vol.  xlvi,  p.  843. 

^  Mandel  and  Levene:  "Zeitschrift  ftir  physiologische  Chemie,"  1906,  Bd. 
xlvii,  p.  151. 


272  SCIENCE    OF   NUTRITION. 

Kossel  and  Steudel  *  point  out  the  fact  that  the  purin  bases 
contain  the  pyramidin  nucleus,  and  that  cytosin,  for  exam- 
ple, needs  only  cyanic  acid,  CONH,  and  an  atom  of  oxygen, 
to  convert  it  into  uric  acid. 

They  query  whether  the  pyramidin  bases  are  precursors  or 
metaboHzed  products  of  the  purins. 

Horbaczewski '  was  the  first  to  note  that  the  ingestion  of 
nucleins  largely  increased  the  uric  acid  in  the  urine.  Food  free 
from  nuclein  has  not  this  effect.  He  also  found  that  if  fresh 
spleen  pulp,  which  contains  no  uncombined  purin  bases,  be 
permitted  to  putrefy,  xanthin  and  hypoxanthin  made  their  ap- 
pearance. If  now  the  pulp  was  shaken  in  the  air,  uric  acid  was 
formed  from  the  oxidation  of  the  bases. 

Spitzer^  found  that  when  air  was  passed  through  aqueous 
extracts  of  spleen  and  liver  digested  at  40°  and  with  exclusion 
of  putrefaction,  uric  acid  was  produced.  The  quantity  of 
purin  bases  present  decreased  with  the  increased  formation 
of  uric  acid.  Purin  bases  added  to  such  a  digest  were  converted 
into  uric  acid,  hypoxanthin  and  xanthin  readily  and  almost 
completely,  and  guanin  and  adenin  with  greater  difficulty. 
This  work  established  the  presence  of  oxidizing  enzymes,  the 
xanthin  oxidazes,  which  could  act  on  the  purin  bases  in  the  or- 
ganism converting  them  into  uric  acid. 

Minkowski*  has  shown  that  if  a  man  be  given  hypoxanthin, 
the  quantity  of  uric  acid  increases  in  his  urine.  He  also  showed 
that  if  a  man  ingest  thymus  gland,  the  nuclein  of  which  yields 
principally  adenin,  the  amount  of  uric  acid  is  increased  in  the 
urine.  If  the  thymus  be  given  to  a  dog,  the  uric  acid  plus 
allantoin  elimination  is  increased.  Allantoin  is  an  oxidation 
product  of  uric  acid  more  frequently  found  in  dog's  than  in 
human  urine.  Minkowski  discovered  finally  that  adenin,  when 
administered  to  a  dog,  did  not  increase  the  uric  acid  elimination, 

'Kossel  and  Steudel:  "Zeitschrift  fiir  Physiologic,"  1903,  Bd.  xxxviii,  p.  49. 
'  Horbaczewski :    "  Sitzungsberichte    der    Wiener    Academie    der    Wissen- 
schaft,"  1891,  Bd.  c,  Abth.  iii,  p.  13. 

'  Spitzer:  "Pfliigcr's  Archiv,"  1899,  Bd.  Ixxvi,  p.  192. 

*  Minkowski:  "Archiv  fiir  ex.  Path,  und  Pharm.,"  1898,  Bd.  xU,  p.  375. 


PURIN   METABOLISM. GOUT.  273 

and  was  not  excreted  as  such,  but  on  autopsy  of  the  dog  the 
uriniferous  tubules  were  found  to  contain  crystals  the  chemical 
structure  of  which  showed  them  to  be  aminodioxypurin.  In 
other  words,  adenin  administered  combined  in  nucleic  acid 
loses  its  amino  (NH2)  group,  receives  three  atoms  of  oxgyen, 
and  is  thereby  converted  into  uric  acid;  adenin  administered  as 
such  receives  two  atoms  of  oxygen  but  does  not  lose  its  NHj 
group  at  the  point  for  the  attachment  of  the  third  atom  of  oxygen. 
This  work  attests  a  varying  behavior  of  purin  bodies  in  accord- 
ance with  their  method  of  chemical  union  w^ith  other  substances, 
and  offers  a  suggestive  key  to  certain  relations  observed  in  gout 
(p.  284).  When  theophylHn,  caffein,  and  theobromin,  the 
methylated  purins  found  in  tea,  coffee,  and  cocoa,  are  ingested 
they  are  not  oxidized  to  uric  acid,  but  they  increase  the  purin 
bases  in  the  urine.^ 

The  original  investigations  of  Horbaczewski  have  recently 
been  considerably  extended  by  Schittenhelm  and  by  Walter 
Jones,  especially  in  regard  to  their  explanation  along  lines  of 
enzymotic  activity. 

Jones  and  Partridge^  find  that  although  the  great  majority 
of  the  organs  of  the  body,  when  self-digested  at  40°  (autolysis), 
convert  guanin  and  adenin  into  xanthin  and  hypoxanthin, 
presumably  through  the  action  of  enzymes,  extracts  of  the  spleen 
of  the  pig  cannot  convert  guanin  into  xanthin,  although  they 
can  convert  adenin  into  hypoxanthin.  Jones  therefore  con- 
cludes that  an  enzyme,  guanase,  which  normally  removes  the 
NHj  group  and  replaces  it  with  O,  is  wanting  in  the  pig's 
spleen,  while  adenase,  the  enzyme  acting  on  adenin  in  a  similar 
fashion,  is  present  there.     Such  a  reaction  would  read: 

CsHjX^NHj  +  H2O  =  CsH^N.O  +  NH3 
Adenin.  Hypoxanthin. 

Investigating  the  subject  further,  the  authors  found  that  the 

^  Kriiger  and  Schmid:  "Zeitschrift  fiir  physiologische  Chemie,"  1901,  Bd. 
xxxii,  p.  104. 

*  Jones  and  Partridge:  Ibid.,  1904,  Bd.  xlii,  p.  343;  see  also  Levene:  "Amer- 
ican Journal  of  Physiology,"  1904,  vol.  xii,  p.  276. 
18 


274  SCIENCE   OF   NUTRITION. 

pancreas  contained  the  cnzjTne,  guanase,  which  converts  guanin 
into  xanthin. 

Sir  Lauder  Brunton'  says  that  Stockvis,  of  Amsterdam,  in 
i860,  found  that  crushed  tissue  had  the  power  to  destroy  uric 
acid.  This  question  has  recently  come  into  prominence  and 
it  has  been  shown  that  different  organs  have  different  powers 
in  this  regard,  and  that  the  same  organ  in  animals  of  different 
species  may  behave  quite  differently. 

Ascoli  ^  found  that  crushed  dog's  liver  had  the  power  to  de- 
stroy uric  acid. 

Wiener^  showed  that  dog's  liver  and  pig's  liver  destroyed  uric 
acid,  whereas  calf's  liver  l"i,ad  less  power  to  do  so,  or  none  at  all. 
The  kidney  pulp  of  various  animals  also  destroyed  uric  acid. 

Schittcnhelm*  finds  that  in  cattle  the  spleen,  lungs,  liver, 
intestine  and  kidney  have  the  power  of  converting  purin  bases 
into  uric  acid  in  the  presence  of  a  constant  oxygen  supply. 
He  finds  a  complete  transformation  of  adenin,  as  follows: 
adenin,  hj'poxanthin,  xanthin,  uric  acid.  Guanin  in  like  man- 
ner becomes  xanthin  and  this  again  is  converted  into  uric  acid. 
He  finds  also  that  extracts  of  the  spleen,  intestines  and  lungs 
have  no  powxr  to  destroy  uric  acid  as  formed  w^ithin  them,  but 
that  the  kidney,  muscle,  and  liver  extracts  possess  the  power  to 
destroy  the  new-formed  uric  acid. 

Schittenhelm^  in  another  paper  finds  that  kidney  extracts 
from  cattle,  through  which  oxygen  is  passed,  may  completely 
destroy  uric  acid  through  a  uricolytic  enzyme. 

It  has  been  showTi  by  Pfeiffer^  that  the  pulps  of  human 
kidneys  and  pigs'  kidneys  have  the  power  to  destroy  uric  acid 
completely,  while  dogs'  kidneys  have  only  a  Hmited  capacity 
in  this  regard. 

*  Lauder  Bninton:  "  Centralblatt  fiir  Physiologic,"  1905,  Bd.  xix,  p.  5. 
^  Ascoli:  "Pfliiger's  Archiv,"  1898,  Bd.  Ixxii,  p.  340. 

'  Wiener:  "Archiv  fiir  ex.  Path,  und  Pharm.,"  1899,  Bd.  xlii,  p.  375. 

*  Schittenhelm:  "Zeitschrift  fiir  physiologische  Chemie,"  1905,  Bd.  xlv, 
p.  145- 

*Schittenhelm:  Ibid.,  1905,  Bd.  xlv,  p.  161. 

*  Pfeiffer:  "Hofmeister's  Beitriige,"  1905,  Bd.  vii,  p.  463. 


PURIN   METABOLISM. GOUT,  275 

Almagia^  finds  that  in  the  horse  the  greatest  power  of  uric 
acid  destruction  is  possessed  by  the  Hver,  and  then  follow  in 
order  of  diminishing  activity  the  kidney,  lymphatic  glands, 
leukocytes,  muscles,  bone-marrow,  spleen,  and  thyroid.  In 
other  organs,  like  the  brain  and  the  pancreas,  the  conditions  are 
such  as  indicate  a  non-destruction  of  uric  acid,  which  is  produced 
by  the  oxidation  of  purin  bases  within  them.  Whenever  uric 
acid  was  destroyed  in  the  above  experiments,  Almagia  found 
that  glyoxyhc  acid  (HOOC-CHO)  was  always  present  in  the 
extract. 

Summarizing  these  results  it  may  be  said  that  nuclein  may 
be  broken  up  by  nuclease,  a  ferment  found  in  all  tissue.  On 
the  liberation  of  the  purin  bases,  guanin  and  adenin  are  denitro- 
genized  by  guanase  and  adenase  wherever  these  enzymes  are 
found.  Oxidizing  enz}Tnes,  the  xanthin  oxidazes,  now  convert 
hypoxanthin  and  xanthin  into  uric  acid,  while  a  uricolytic  fer- 
ment of  varying  potency  in  different  tissues  and  in  different 
animals  may  break  up  and  destroy  the  uric  acid.  That  pro- 
cesses akin  to  these  go  on  w^ithin  the  living  organs  of  the  body  is 
now  generally  beheved,  and  the  following  animal  experiments 
tend  to  confirm  this  doctrine,  although  it  will  become  evident 
that  the  uricolytic  power  of  kidney  extracts,  so  frequently  men- 
tioned above,  appears  to  be  entirely  overshadowed  in  the  living 
kidney  by  the  function  of  uric  acid  eUmination. 

It  has  already  been  stated  that  the  ingestion  of  hypoxanthin 
by  a  man  increased  the  uric  acid  output  in  the  urine.  It  has 
long  been  knovwi  that  if  uric  acid  be  given  per  os,  or  subcuta- 
neously,  it  may  in  greater  part  be  converted  into  urea,  and  in 
part  eliminated  in  the  urine.  The  quantity  eliminated  varies 
in  different  animals.  Salkowski  ^  finds  that  uric  acid  given  to 
dogs  is  mostly  eliminated  as  urea,  although  17.7  per  cent, 
appears  in  the  urine  in  the  form  of  allantoin.  When  uric  acid 
is  given  to  rabbits  the  urine  contains  urea,  allantoin  and  some 

*  Almagia:  "Hofmeister's  Beitrage,"  1905,  Bd.  vii,  p.  459. 

*  Salkowski:  "Zeitschrift  fiir  physiologische  Chemie,"  1902,  Bd.  xxxv, 
P-  495- 


276  SCIENCE   OF   NUTRITION. 

uric  acid.  Mendel  and  White '  found  that  allantoin  was  eUmi- 
nated  in  the  urine  of  cats  and  dogs  after  intravenous  injection 
of  urates.  It  is  thus  apparent  that  uric  acid  is  readily  destroyed 
in  these  animals  and  only  a  small  quantity  of  a  first  oxidation 
product,  allantoin,  appears  in  the  urine.  Allantoin  is  not  nor- 
mally found  in  human  urine.  Glyoxylic  acid,  which  has  al- 
ready been  mentioned  as  constantly  found  when  uric  acid  is 
destroyed  in  autolyzing  tissue,  is  a  substance  which  may  be 
produced  by  treating  allantoin  with  alkali.  It  has  also  been 
found  in  the  urine  of  rabbits  after  intraperitoneal  injection  of 
from  2  to  5  grams  of  uric  acid,  and  it  has  been  detected  in  the 
urine  of  a  gouty  patient.^ 

Schittenhelm  and  Bendix^  have  injected  rabbits  subcuta- 
neously  and  intravenously  with  guanin,  and  have  found  uric  acid 
in  greatly  increased  quantity  in  the  urine,  together  with  xanthin, 
which  is  normally  absent  in  rabbits.  The  experiment  indicates 
the  metabolism  of  guanin  intra-vitam,  according  to  processes 
already  observed  in  vitrco.  If  an  Eck  fistula,  which  excludes 
the  portal  blood  from  the  liver,  be  made  in  a  dog,  uric  acid  ap- 
pears in  considerable  quantity  in  the  urine,  which  indicates 
that  uric  acid  is  normally  oxidized  in  the  dog's  liver.^ 

Burian  and  Schur,^  after  careful  perusal  of  the  literature 
and  of  their  own  work,  came  to  the  conclusion  that  each  variety 
of  animal  had  a  specific  capacity  for  burning  purin  bodies 
ingested.  They  found  a  constant  elimination  in  dog's  urine 
of  one-twentieth  part  of  the  purins  ingested,  one-sixth  part  in  the 
case  of  rabbits,  and  one-half  in  the  case  of  man.  They  describe 
how  Minkowski,  after  giving  a  man  hypoxanthin,  saw  that 
48.6  per  cent,  of  it  was  eUminated  as  uric  acid;  how  Burian 


'  Mendel  and  White:    "American  Journal  of  Phvsiologv,"   1904,  vol.   xii, 
p.  85. 

*  Almagia:  Loc.  cit. 

^Schittenhelm  and  Bendix:  "Zeitschrift  fiir  physiologische  Chcmie,"  1905, 
Bd.  xliii,  p.  365. 

*  Hahn,  Massen,  Nehcki,  and  Pawlow:  "  Archiv  fiir  ex.  Path,  und  Pharm.," 
1893,  Bd.  xxxii,  p.  191. 

*  Burian  and  Schur:  "Pfliiger's  Archiv,"  1901,  Bd.  l.x.xxvii,  p.  239. 


PURIN  METABOLISM. GOUT.  277 

repeated  the  experiment  with  the  result  that  46,2  per  cent, 
appeared  as  uric  acid;  how  the  subject  of  the  last  experiment 
ehminated  51. i  and  53.8  per  cent,  of  the  purins  contained  in  a 
meat  diet,  and  52.6  and  52.9  per  cent,  of  those  contained 
respectively  in  calf's  Hver  and  calf's  spleen.  Therefore,  Burian 
and  Schur  multipHed  the  purin  excretion  of  a  man  by  two  and 
of  a  dog  by  twenty  in  order  to  determine  the  total  purin  metab- 
oKsm.  They  called  these  numbers  the  integral  factors  of  purin 
excretion.  The  cause  of  the  size  of  the  integral  factor  will  be 
discussed  later. 

It  has  been  made  clear  that  the  purin  bodies  may  be  derived 
from  ingested  nucleins,  but  this  cannot  be  the  only  source, 
since  purins  are  found  in  the  urine  during  starvation  and  on 
a  diet  free  from  purins.  This  indicates  a  constant  production 
of  these  substances  in  metabolism,  it  has  been  thought,  through 
the  destruction  of  cell  nuclei.  Uric  acid  and  purin  bases  from 
this  source  have  been  termed  endogenous  by  Burian  and  Schur, 
in  contradistinction  to  those  which  are  ehminated  after  the 
ingestion  of  nuclein-containing  food  which  are  called  exogenous. 

Burian  and  Schur  ^  also  estabhshed  the  fact  that  while  the 
endogenous  uric  acid  elimination  varied  between  0.3  and  0.6 
grams  daily,  according  to  the  individual,  it  did  not  vary  in  the 
same  individual  but  was  a  constant  factor  of  his  metabohsm. 

A  purin-free  diet  is  obtained  by  giving  such  articles  of  food 
as  milk,  eggs,  bread,  potatoes,  fats,  and  sugars,  none  of  which 
contain  nuclear  material  which  forms  exogenous  purins  in  the 
body.  Burian  and  Schur  found  that  on  such  a  diet  the  uric 
acid  elimination  was  entirely  independent  of  the  quantity  of 
proteid  ingested.  It  has  been  demonstrated  by  Rockwood^ 
that  the  endogenous  uric  acid  ehmination  is  independent  of  the 
calorific  value  of  the  diet.  Addition  of  500  calories  contained 
in  maple  sugar  to  a  diet  containing  2500  calories  did  not  affect 
the  excretion  of  uric  acid.  Rockwood's  experiments  extended 
over  a  long  period  of  time.     His  individuals  wxre  nourished  on 

^  Burian  and  Schur:  Loc.  cit. 

^  Rockwood:  "American  Journal  of  Physiology,"  1904,  vol.  xii,  p.  38. 


278  SCIENCE  OF   NUTRITION. 

milk,  eggs,  white  bread,  crackers,  cheese,  apples,  and  butter. 
The  constancy  of  the  uric  acid  output  in  the  same  individual  is 
seen  in  the  following  table, — in  one  case  the  record  covering 
nearly  a  year : 

TABLE  SHOWING  THE  CONSTANCY  OF  THE  DAILY  ENDOG- 
ENOUS URIC  ACID  EXCRETION  IN  THE  SAME  INDIVIDUAL 
(TWO  SUBJECTS). 

Person,  A.            Date,  1903.            Xix  Urine,  Grams.  Uric  .\riD,  Grams. 

January 1 1  -99  0.308 

February 11-58  0305 

March 11. 15  o-3i5 

May 12.63  0.321 

July 12.68  0-313 

November 9.99  0.298 

Person,  B.  January- 13.41  0.478 

March 13-92  0.452 

This  total  shows  the  constancy  of  the  output  of  endogenous 
uric  acid  in  the  same  individual  during  a  long  period.  Here 
the  difference  in  the  behavior  of  two  individuals  might  possibly 
be  ascribed  to  a  personal  idiosyncrasy  as  regards  the  uricolytic 
power  of  the  subject,  or  to  a  difference  in  the  capacity  of  pro- 
ducing uric  acid.  From  the  record  of  Chittenden's  ^  experiments, 
which  covered  a  period  of  twenty-one  months,  it  may  be  ob- 
served that  a  very  low  proteid  diet  and  moderate  intake  of  food 
were  without  effect  on  the  output  of  uric  acid. 

Burian  and  Schur^  have  made  a  series  of  experiments  as 
regards  the  cause  of  the  "integral  factor"  of  purin  metabolism, 
which  has  already  been  defined.  They  find  that  a  part  of  the 
endogenous  purins  are  burned  in  metabolism,  for  the  uric  acid 
elimination  in  the  dog  rises  largely  after  cutting  the  liver  from 
the  circulation  by  means  of  an  Eck  fistula.  They  note  that  no 
one  has  been  able  to  find  uric  acid  in  normal  blood.  They 
desired  to  see  if  uric  acid  would  accumulate  in  the  blood  if  the 
kidneys  were  both  extirpated.  No  such  result  followed  nephrec- 
tomy in  a  dog.  The  purin  bodies  were  apparently  completely 
burned.     They  then  extirpated  the  kidneys  and  ligated  the 

'  Chittenden:  "Physiological  Economy  in  Nutrition,"  1904,  p.  24, 
'  Burian  and  Schur:  Loc.  cit. 


PURIN   METABOLISM. — GOUT.  279 

aorta  at  a  point  just  above  the  celiac  artery.  The  operation  cut 
off  the  Hver  and  intestine  from  the  circulation.  Under  these 
circumstances  uric  acid  accumulated  in  the  blood  because  its 
destruction  was  not  accomplished  by  the  liver.  The  question 
arises:  If  the  normal  organism  can  completely  destroy  all 
purins,  why  should  a  definite  fraction  be  continually  ehminated 
in  the  urine?  Burian  and  Schur  beheve  that  endogenous 
purins,  formed  in  the  tissues,  are  oxidized  therein  to  uric  acid,  and 
in  so  far  as  this  substance  is  carried  to  such  organs  as  the  liver, 
it  is  destroyed,  but  in  so  far  as  it  passes  through  the  renal 
arteries,  it  is  removed  by  the  kidney.  In  confirmation  of  this 
they  show  that  a  diuretic  which  increases  the  blood-flow  to  the 
kidney  likewise  increases  the  uric  acid  elimination,  without 
affecting  the  other  nitrogen  constituents  of  the  urine.  Possibly 
the  fall  in  uric  acid  elimination  noted  by  Mandel  in  aseptic 
fever  (p.  267,  Fig.  10)  may  be  similarly  due  to  a  constriction 
of  the  renal  vessels  which  always  accompanies  fever. 

Burian  and  Schur  conclude  that  of  the  mass  of  blood  which 
receives  uric  acid  from  the  tissues  in  man,  the  same  amount 
flows  through  the  organs  which  destroy  uric  acid  as  flows 
through  the  kidney,  and  hence  the  integral  factor  of  two.  On 
the  other  hand,  the  relation  between  the  volume  of  kidney 
blood  and  the  volume  of  blood  passing  through  the  organs 
which  destroy  uric  acid  in  dogs,  must  be  as  i :  20  in  order  to 
explain  the  integral  factor  twenty.  At  first  sight  this  does  not 
explain  why  exogenous  purins,  which  must  pass  from  the 
intestine  to  the  dog's  liver,  should  escape  complete  destruction 
in  that  organ.  Burian  and  Schur,  however,  have  shown  that 
whereas  uric  acid  given  per  os  is  almost  completely  destroyed 
in  the  dog,  the  purin  bases  or  nuclein  digestive  products  con- 
taining them  apparently  pass  through  the  Hver  to  be  oxidized 
to  uric  acid  elsewhere. 

The  liver  has  the  power  of  oxidizing  uric  acid  but  not  the 
bases.  Hence  the  behavior  of  exogenous  purins  must  be 
exactly  the  same  as  if  they  arose  in  the  general  metabolism 
of  the  tissues  themselves  and  were  oxidized  to  uric  acid,  which 


28o  SCIENCE   OF  NUTRITION. 

was  then  carried  in  definite  fractions,  in  accordance  with  the 
relative  volume  of  the  blood  supply,  either  to  the  kidney  for 
elimination  or  to  the  organs  where  uric  acid  is  destroyed. 

This  explanation  of  the  cause  of  the  integral  factor  would 
explain  the  results  of  Loewi/  which  showed  that  the  ingestion 
of  the  same  amount  of  nuclein-containing  food  by  different 
people  resulted  in  the  excretion  of  the  same  increased  quantity 
of  uric  acid  in  the  urine. 

The  source  of  the  endogenous  purins  has  been  the  cause  of 
considerable  speculation.  In  birds  there  is  a  large  synthetic  pro- 
duction of  uric  acid  in  the  hver,  for  jMinkowski  ^  has  sho\\Ti  that 
extirpation  of  the  hver  in  geese  leads  to  a  replacement  of  uric 
acid  by  ammonia  and  lactic  acid  in  the  urine. 

Wiener  ^  has  suggested  that  there  is  a  synthetic  formation  of 
uric  acid  in  the  mammahan  organism  from  urea  and  tatronic 
acid  according  to  the  following  formulae: 


NHj 

COOH 

1 

HN— CO 

1       1 

i 

CO 
1 

+ 

CHOH 

OC     CHOH  +   2H2O 

1       1 

I 

Urea. 

COOH 
Tatronic  Acid. 

1       1 
HN— CO 

Dialuric  Acid. 

HN     — 

1 

CO 

1 

NH2 

HN     —     CO 

1                  1 

HN    — 

CHOH 
CO 

1 
+     CO     = 

1 

NH, 

OC             C  —  NH 

1              II               >CO  +  2  H2O 
HN    —    C  —  NH 

Uric  Acid. 

Burian,*  however,  has  demolished  this  theory  by  showing 
that  although  tissue  extracts  when  digested  with  either  tatronic 
or  dialuric  acid  oxidize  xanthin  to  uric  acid  more  readily  than 
without  them,  still  there  is  absolutely  no  formation  of  uric  acid 
except  from  purin  compounds  present. 

Ingestion  of  pyramidin  bases  (p.  272)  has  also  failed  to 
yield  purins  in  the  organism.^ 

*  Loewi:  ".\rchiv  fiir  ex.  Path,  und  Pharm.,"  1900,  Bd.  xliv,  p.  i. 
^Minkowski:  Ibid.,  1886,  Bd.  xxi,  p.  41. 

'  Wiener:  "Hofmeister's  Beitrage,"  1902,  Bd.  ii,  p.  42. 

^Burian:  "Zeitschrift  fiir  physiologische  Chemie,"  1905,  Bd.  xliii,  p.  526. 

*  Steudel:  Ibid.,  1903,  Bd.  xx.xix,  p.  136. 


PURIN   METABOLISM. GOUT.  281 

Burian  ^  has  investigated  the  source  of  the  endogenous  purins 
and  comes  to  the  conclusion  that  only  a  small  part  of  the  en- 
dogenous uric  acid  arises  from  the  nucleo-proteids  of  cellular 
tissue  or  those  of  dead  leukocytes.  It  would  require  too  large 
a  destruction  of  tissue  to  provide  from  0.3  to  0.6  gram  uric 
acid  or  o.i  to  0.2  gram  purin  nitrogen  daily  in  the  urine  if  it 
all  arose  from  cell  nuclein. 

Burian  and  Schur's^  analyses,  showing  the  content  of  purin 
nitrogen  in  various  tissues,  is  given  below: 

TABLE  SHOWING  THE  QUANTITY  OF  PURIN  N  CONTAINED  IN 
100  GRAMS  OF  DIFFERENT  ANIMAL  TISSUES. 

Total  Pdrin  N.        N  in  Free  Purin  Bases. 

Meat 0.06  0-04S 

Thymus 0.45  0.05 

Calf  s  liver 0.12  0-033 

Calf's  spleen 0.16  0.046 

To  obtain  the  amount  of  endogenous  uric  acid  present  in  the 
urine,  if  it  were  produced  by  the  destruction  of  nucleo-proteids, 
it  would  be  necessary  to  completely  destroy  nuclein  to  the  extent 
of  that  contained  in  more  than  loo  grams  of  liver.  It  does  not 
seem  possible  that  nuclein  destruction  or  nuclein  metaboHsm 
could  reach  this  extent. 

The  experiments  of  Burian^  consisted  in  perfusing  dog's 
muscles  with  blood  free  from  uric  acid.  He  noticed  that  after 
the  perfusion  of  such  blood  through  the  muscles,  uric  acid  was 
constantly  found  in  it.  If  the  muscle  was  caused  to  contract 
during  the  perfusion,  a  very  considerable  increase  in  the  quan- 
tity of  the  purin  bases  was  found  in  the  blood  and  there  was  an 
increase  in  the  quantity  of  these  bases  found  in  the  muscles 
themselves. 

Burian  concludes  that  in  the  resting  muscle  there  is  a  con- 
stant production  of  hypoxanthin  which  is  converted  into  uric 
acid  through  the  activity  of  the  xanthin  oxidase.  In  the  active 
muscle  there  is  a  greater  production  .of  hypoxanthin  which  is 
not  completely  oxidized  on  account  of  a  local  oxygen  deficiency. 

^  Burian:    "Pfluger's  Archiv,"  1905,  Bd.  xliii,  p.  532. 
^  Burian  and  Schur:  Ibid.,  1900,  Bd.  Ixxx,  p.  308. 
^  Burian:  Loc.  cit. 


282  SCIENCE  OF   NUTRITION. 

It  had  been  found  by  many  previous  observers  that  exercise 
has  no  effect  on  the  purin  excretion  in  the  urine  of  twenty-four 
hours  in  man.  Burian,  however,  finds  a  large  increase  in  the 
purin  elimination  for  an  hour  of  two  after  severe  muscular 
exercise,  and  this  is  followed  by  a  compensatory  reduction  in 
the  output  during  those  subsequent  hours  which  represent  the 
interval  of  weariness  in  the  muscle. 

These  observations  were  confirmed  by  the  work  of  Rockwood,^ 
who  saw  that  the  purin  excretion  was  less  during  the  night  than 
during  the  day,  and  by  the  work  of  Pfeil,^  who  found  a  constant 
morning  rise  in  the  output  of  purins  in  human  urine. 

These  facts  confirm  Burian's  contention  that  the  most 
general  source  of  endogenous  purins  is  a  constant  production 
of  hypoxanthin  in  muscle,  a  production  which  varies  with  the 
individual  and  is  possibly  proportional  to  the  mass  of  his  mus- 
culature. Comparable  to  this  is  the  constant  production  of 
creatin  (p.  118).  Hypoxanthin  is  oxidized  to  uric  acid  in  the 
muscle,  and  uric  acid,  if  carried  to  the  liver,  which  is  certainly 
the  principal  organ  for  its  destruction,  may  there  be  oxidized. 
Such  of  the  purin  bases  as  escape  oxidation  may  be  excreted 
by  the  blood  flowing  through  the  kidney,  even  as  uric  acid  is 
excreted  under  the  same  circumstances. 

Just  as  the  whole  trouble  in  diabetes  turns  upon  the  in- 
ability of  the  organism  to  destroy  sugar,  so  the  symptoms  mani- 
fested in  gout  are  dependent  upon  the  deposit  of  acid  urate  of 
sodium  in  certain  localities.  One  of  the  earliest  descriptions  of 
gout  comes  from  Sydenham,  who  suffered  for  forty  years  from 
the  disease  and  published  an  extended  account  of  it  in  1683. 
It  was  Garrod^  who  first  estabhshed  the  fact  that  uric  acid  was 
present  in  the  blood  of  gouty  persons.  He  beheved  that  this 
excess  of  urate  was  the  cause  of  gout,  the  excess  being 
deposited  from  the  blood  in  the  joints  in  the  form  of  crystals. 
The  problem  of  metabolism  in  gout  is  a  problem  of  the  fac- 

*  Rockwood:  Loc.  cil. 

'Pfeil:  "Zeitschrift  fur  physiologische  Chemie,"  1904,  Bd.  xl,  p.  i. 

'  Garrod:  "The  Nature  and  Treatment  of  Gout,"  1859. 


PUREST   METABOLISM. GOUT.  283 

tors  entering  into  the  cause  of  this  deposit  of  urate.  The 
general  metaboHsm,  exclusive  of  the  purin  factor,  is  exactly  the 
same  as  in  health.  Magnus-Levy  ^  proved  that  the  oxygen 
absorption  and  carbon  dioxid  elimination  is  the  same  in  gout  as 
in  health.  The  cause  of  the  trouble  must  be  sought  elsewhere 
than  in  a  reduced  general  oxidation  power  of  the  tissues. 

Clinical  experience  teaches  that  the  predisposing  causes  are 
excessive  eating,  little  muscular  exercise,  the  abuse  of  alcoholic 
beverages,  and  lead-poisoning. 

Beebe"  has  administered  alcohol  in  various  forms  to  a  normal 
individual.  He  finds  that  even  large  doses  have  no  effect  on  the 
hourly  excretion  of  uric  acid  in  a  fasting  man.  The  endogenous 
purin  metabolism  is  therefore  unchanged  by  the  ingestion  of 
alcohol.  It  is  important  to  know  that  alcohol  is  apparently 
without  effect  upon  such  part  of  the  purins  as  may  be  directly 
derived  from  cell  metabolism.  On  the  other  hand,  when 
alcohol  is  given  with  nuclein- containing  food,  the  uric  acid 
elimination  rises  markedly.  It  was  found  that  port  wine  w^as 
more  potent  in  this  regard  than  a  larger  quantity  of  alcohol 
taken  in  a  purer  form.  The  addition  of  350  c.c.  of  port  wine 
on  two  successive  days  to  a  mixed  diet  which  had  been  constantly 
maintained  for  several  days,  caused  a  rise  in  uric  acid  ehmi- 
nation  from  0.5  gram  to  0.7  gram  on  the  first  day  of  port  wine 
ingestion,  and  to  0.8  gram  on  the  second  day,  while  the  fol- 
lowing alcohol-free  day  showed  an  elimination  of  only  0.55 
gram.  Beebe  ascribed  this  action  to  a  reduction  of  uricolytic 
power  in  the  liver. 

Minkowski,^  with  a  master  hand,  summarizes  modem 
knowledge  concerning  gout  as  follows : 

I.  The  deposit  of  urate  in  the  tissues  is  the  first  evidence 
of  the  formation  of  the  specific  gouty  nodules.  These  tissues 
are  not  necrotic,  as  taught  by  Ebstein. 

'  Magnus-Levy:  "Berliner  klinische  Wochenschrift,"  1896,  No.  xix,  p   416. 
'  Beebe:  "American  Journal  of  Physiolog}^"  1904,  vol.  xii,  p.  13. 
^Minkowski:  von  Leyden's  "Handbuch  der  Emahrungstherapie,"   1904, 
Bd.  ii,  p.  277. 


284  SCIENCE   OF  NUTRITION. 

2.  The  tissue  changes  in  the  vicinity  of  the  gouty  nodules 
are  in  part  due  to  mechanical,  in  part  to  chemical  or  osmotic 
action,  caused  by  the  precipitated  urates. 

3.  The  acute  inflammation  in  gout,  as  observed  during  the 
attack,  is  produced  in  the  vicinity  of  the  urate  deposits  through 
some  unknown  cause.  Traumatic,  toxic,  or  infectious  elements 
appear  to  be  collectively  active  in  this  regard.  The  attack 
probably  constitutes  the  reaction  of  the  organism  to  rid  itself 
of  uric  acid,  an  effect  which  is  only  partly  realized. 

4.  An  accumulation  of  uric  acid  in  the  blood  is  a  constant 
accompaniment  of  gout. 

5.  The  increased  quantity  of  uric  acid  in  the  blood  must  not 
be  considered  as  the  cause  of  the  precipitation  of  urates  in  the 
gouty  nodules.  There  must  be  certain  local  influences  which 
favor  the  deposit  of  urates;  for  Klemperer  has  shown  that  the 
blood  of  gouty  patients  may  dissolve  much  more  uric  acid  than 
is  actually  present  in  it;  and  again,  the  blood  in  leukemia  may 
contain  as  much  uric  acid  as  in  gout,  without  there  being  any 
indication  of  a  deposit  of  urate. 

6.  The  uric  acid  elimination  is  the  same  in  the  gouty  as  in 
the  normal  person,  except  at  the  time  of  the  attack.  Before 
the  attack  there  is  retention,  but  during  and  after  the  attack 
an  increased  excretion  of  uric  acid  in  the  urine. 

7.  The  accumulation  of  uric  acid  in  the  blood  is  not  due  to 
a  diminished  oxidation  of  uric  acid,  but  rather  to  a  diminution 
in  the  quantity  excreted  in  the  urine. 

8.  It  is  not  certain  that  the  lessened  excretion  of  uric  acid 
is  due  to  a  disturbance  of  renal  function.  Very  likely  it  depends 
upon  the  presence  of  uric  acid  in  some  abnormal  chemical 
union.  This  abnormal  substance  may  be  with  difficulty  elimi- 
nated in  the  urine,  but  may  lend  itself  readily  to  the  formation 
of  tophi  (p.  273). 

9.  The  ultimate  cause  of  the  unusual  behavior  of  uric  acid 
in  gout  is  probably  an  abnormal  metabolism  within  the  nuclei 
of  the  cells,  where  the  nucleic  acid  content  is  the  means  of  solu- 


PURIN   METABOLISM. — GOUT.  285 

tion  and  conveyance  not  only  of  the  purin  bases  but  also  of 
uric  acid. 

The  opinions  of  other  modem  workers  vary  somewhat  from 
those  of  Minkowski,  as  appears  in  the  following: 

Almagia/  in  Hofmeister's  laboratory,  has  performed  some 
interesting  experiments  and  concludes  that  the  older  view  of 
Garrod  is  correct, — that  is,  that  an  excess  of  urates  in  the  blood 
is  the  cause  of  gout.  Almagia  finds  that  thin  strips  of  cartilage 
suspended  in  dilute  neutral  solutions  of  sodium  urate  absorb 
the  salt,  do  not  destroy  it,  but  cause  it  to  be  deposited  in  fine 
crystals  within  the  cartilage.  He  furthermore  injected  five  to 
seven  grams  of  uric  acid  into  the  peritoneal  cavity  of  rabbits, 
a  dose  which  usually  killed  them.  On  testing  the  liver,  spleen, 
muscles  and  lungs  with  the  murexid  test  for  uric  acid,  negative 
results  were  obtained,  whereas  cartilage  gave  a  positive  reaction 
indicating  the  presence  of  urates.  Almagia  concludes  that 
the  deposit  of  urates  in  the  cartilage  of  a  gouty  patient  is  but 
the  result  of  a  temporary  or  permanent  increase  in  the  uric  acid 
content  of  the  blood. 

The  work  of  Soetbeer^  is  of  the  best  modern  character,  and 
it  confirms  the  older  view  of  Garrod  that  the  cause  of  gout  is  a 
retention  of  uric  acid.  Soetbeer  compared  the  excretion  of 
uric  acid  by  gouty  people  during  three-hour  intervals  with  that 
of  normal  individuals,  as  observed  by  Pfeil  (p.  282).  In  one 
case  of  long  standing  gout,  of  light  character  and  with  long 
intervals  between  the  attacks,  there  was  little  variation  from 
the  normal  in  the  uric  acid  excretion.  In  another  case  of  gout, 
a  patient  who  was  examined  between  the  attacks  showed  no 
increase  in  uric  acid  output  after  changing  from  a  purin-free 
diet  to  one  containing  320  grams  of  meat,  and  showed  only  a 
slight  increase  in  elimination  after  640  grams  of  meat  were 
given.  These  results  were  obtained  six  wTeks  after  the  last 
attack  and  at  a  time  when  the  patient  was  entirely  free  from  pain. 
In  still  another  case  350  grams  of  meat  were  given  during  the 

^  Almagia:  "Hofmeister's  Beitrage,"  1905,  Bd.  vii,  p.  466. 

^Soetbeer:  "Zeitschrift  fiir  physiologische  Chemie,"  1904,  Bd.  xl,  p.  54. 


286  SCIENCE   OF  NUTRITION. 

attack  to  a  gouty  patient  who  had  no  fever  and  whose  urine  was 
free  from  albumin  and  sugar.     The  results  were  as  follows: 

Uric  Acid 
IN  Grams. 

Diet  free  from  purins 0.276 

Diet  free  from  purins 0.328 

Diet  +350  grams  meat 0.316 

"       "  "         "     0.270 

"       "  "         "    0.255 

In  this  experiment  even  during  the  days  of  purin-frce  diet 
there  was  no  "morning  rise"  noted  as  a  normal  incident  by 
Pfeil.  The  hourly  uric  acid  excretion  was  very  even.  The 
kidney  was  apparently  removing  uric  acid  up  to  the  limit  of  its 
capacity.  This  work  renders  it  probable  that  uric  acid  retention 
is  the  cause  of  gout. 

Von  Noorden  and  Schliep^  suggest  that  gouty  patients  be 
tested  for  their  "tolerance"  for  purin  bodies  just  as  diabetics 
are  tested  for  their  tolerance  for  carbohydrates.  Four  hundred 
grams  of  meat  contain  0.24  gram  of  purin  nitrogen,  of  which  in 
the  normal  person  one-half  is  oxidized  and  one-half  eliminated 
in  the  urine — 0.24  gram  N  =  0.72  gram  uric  acid.  A 
patient  was  put  on  a  purin-free  diet;  was  given  400  grams  of 
meat,  then  put  on  a  purin-free  diet  again,  and  afterwards  was 
tested  with  200  grams  of  meat.     The  results  were  as  follows: 

Uric  Acid 
Day.  Diet.  in  Grams. 

4 Purin-free 0.462 

5 "        "      -f- 400  g.  meat -0.522 

6 "        "      -f  400  g.  meat. ..  .0.544 

7 "        "    0.539 

8 "        "    0.528 

9 "  "    0.458 

10 "  "      -|-2oog.meat -0.549 

II "  "      -|- 200  g.  meat -0.655 

12 "  "    0.647 

13 "  "    0.499 

14 "  "    0.433 

The  authors  conclude  that  while  the  increased  uric  acid 
output  after  giving  400  grams  of  meat  is  not  what  it  would  be 

'Von  Noorden  and  Schliep:  "Berliner  klinische  Wochenschrift,"  1905, 
Bd.  xlii,  p.  1297. 


PURIN   METABOLISM. — GOUT.  287 

normally,  yet  after  giving  200  grams  the  quantity  of  additional 
uric  acid  (which  should  amount  to  0.18  gram)  is  fully  ehmi- 
nated.  Hence  this  patient  had  a  tolerance  for  the  purins  in  200 
grams  of  meat. 

Dietetic  rules  for  gouty  sufferers  are  intended  to  combat 
the  fundamental  anomahes  of  the  metabolism.  The  organism 
must  not  be  overloaded  with  uric  acid.  Minkowski's  rules^ 
for  treatment  of  gout  may  be  thus  abstracted:  Sweetbreads, 
liver,  and  kidney  are  to  be  rigidly  excluded  from  the  diet. 
Meat  is  to  be  taken  in  moderation  only.  Wine  should  be  taken 
sparingly  or  not  at  all,  and  beer  rigidly  excluded  on  account  of 
the  nuclein  in  yeast.  Cathartics  may  be  given  to  rid  the  intes- 
tine of  purin  bodies  excreted  into  the  intestinal  canal,  and 
water  drinking,  which  promotes  a  larger  flow  of  urine  and 
increased  uric  acid  elimination,  is  strongly  to  be  commended. 
The  diet  for  a  gouty  patient  should  contain  each  day  100  or 
120  grams  of  proteid,  80  or  100  grams  of  fat,  and  250  or  300 
grams  of  carbohydrates  (2200  to  2600  calories).  This  should 
not  include  more  than  from  200  to  250  grams  of  meat  per  day. 
Indigestible  cakes,  pies,  rich  foods  and  heavy  salads  should  be 
forbidden.  Moderation  and  self-control  are  the  watchwords 
for  the  gouty  sufferer. 

It  is  impossible  to  increase  the  oxidation  of  uric  acid,  and 
no  treatment  now  known  increases  its  solubility.  Minkowski 
hopes  that  some  organic  compound  may  be  discovered  which 
will  accomplish  this  purpose.  He  believes  the  relief  given  by 
preparations  of  the  salicylate  group  is  afforded  only  through 
their  stopping  pain  and  promoting  perspiration. 

Bearing  the  facts  of  the  above  discussion  in  mind,  the 
reader  will  comprehend  that  present  day  doctrines  concerning 
metabolism  in  gout  may  shortly  become  entirely  obsolete 
through  new  and  far-reaching  discoveries. 

^Minkowski:  "Deutsche  medizinische  Wochenschrift,"  1905,  Bd.  xxxi, 
p.  409. 


CHAPTER  XV. 
THEORIES  OF  METABOLISM  AND  GENERAL  REVIEW. 

There  has  been  a  difference  of  opinion  as  to  whether  the  food 
substances  must  first  become  vital  integers  of  the  hving  cell,  or 
whether  the  non-living  food  materials  are  metabolized  without 
ever  becoming  a  constituent  part  of  the  living  protoplasm. 

Pfliiger  held  the  former  view, — that  incorporation  of  nutri- 
tive matter  with  the  living  substance  is  essential  to  its  metab- 
oHsm.  He  conceived  that  living  proteid  may  contain  the  labile 
cyanogen  group  in  contrast  with  dead  proteid  which  contains 
the  amino  group.  He  illustrated  this  by  Wohler's  classic 
experiment  of  the  easy  conversion  of  ammonium  cyanate  into 
urea: 

NH.OCN  =  (HN2)2CO 

Voit's  theory  was  that  the  Hving  proteid  is  comparatively 
stable  and  that  food  proteid  which  becomes  the  circulating  pro- 
teid of  the  blood  is  carried  to  the  cells  and  promptly  metaboHzed. 
The  other  foodstuffs  are  also  burned  without  first  entering  into 
the  composition  of  the  cell. 

A  mass  of  living  cells  composing  the  substance  of  a  warm- 
blooded animal  has  the  same  requirement  of  energy  as  any 
similar  mass  of  living  cells  composing  the  substance  of  any  other 
animal  of  the  same  size  and  shape.  The  reason  for  the  metab- 
oHsm  hes  in  unknown  causes  within  the  cells.  Liebig  conceived 
the  cause  to  be  due  to  the  swinging  motion  of  the  small  con- 
stituent particles  of  the  cells  themselves.  If  this  hypothesis  be 
accepted  the  vibrations  of  the  cells  may  be  assumed  to  shatter 
the  proteid  molecule  into  fragments  consisting  of  amino  bodies, 
and  to  break  down  fat  and  sugar  into  substances  of  a  lower 
order  than  themselves. 


THEORIES    OF   METABOLISM.  289 

The  uniformity  of  the  energy  requirement  is  illustrated  by 
the  fact  that  the  number  of  calories  given  off  during  the  twenty- 
four  hours  by  one  square  meter  of  surface,  in  various  animals 
and  in  man  in  the  condition  of  starvation,  is  the  same. 

Even  in  pathological  conditions  a  remarkable  constancy  of 
total  heat  production  is  apparent.  Thus,  in  such  typical  dis- 
turbances as  anemia,  diabetes,  gout  and  obesity,  the  general 
laws  governing  the  output  of  carbon  dioxid,  the  absorption  of 
oxygen  and  the  production  of  heat,  are  found  to  be  the  same  as 
in  health.  In  fever  the  metaboHsm  and  heat  production  in- 
crease and  this  to  a  large  extent  on  account  of  the  warming  of 
the  cells.  In  exophthalmic  goiter  there  is  probably  an  increase 
in  metaboHsm,  due  to  the  stimulus  of  an  excessive  production 
of  iodothyrin  in  the  thyroid  gland,  while  in  myxedema  the 
absence  of  the  same  substance  causes  a  considerable  reduc- 
tion in  the  metabolism.  Drugs  may  influence  the  course  of 
metaboHsm,  iodothyrin  increasing  it  and  morphin  profoundly 
diminishing  it,  but  on  the  whole  the  most  striking  fact  is 
not  the  variabiHty,  but  rather  the  uniformity,  of  the  processes 
concerned. 

Within  recent  years  the  work  of  Kossel,  Fischer,  Hofmeister, 
Osborne  and  Levene  has  given  a  more  definite  conception  of  the 
composition  of  proteid  than  was  before  possible.  There  is  every 
indication  that  the  proteid  molecule  consists  fundamentally  of 
groups  of  amino  fatty  acids  banded  together.  Proteids  vary 
with  the  integral  components  of  their  chemical  chains.  It  has 
long  been  known  that  the  end  products  of  tryptic  digestion 
include  such  substances,  but  Kutscher  first  showed  that  con- 
tinued tryptic  digestion  resulted  in  the  almost  complete  trans- 
formation of  proteid  into  these  amino  acids.  Cohnheim 
discovered  erepsin,  an  enzyme  derived  from  the  intestinal  wall, 
which  rapidly  converts  albumoses  into  these  substances. 

On  chemical  analysis,  using  methods  developed  in  Emil 
Fischer's  laboratory,  the  cleavage  products  of  various  proteids 
appear  distributed  as  shown  in  the  following  table,^  in  w^hich 

*  Abderhalden,  E.:  "Zeitschr.  f.  physiol.  Chem.,"  1905,  Bd.  xliv,  p.  17. 
19 


290 


SCIENCE   OF   NUTRITION. 


the  figures  given  for  globin  represent  the  recovery  of  70  per 
cent,  of  the  constituents  of  its  molecule: 

COMPOSITION  OF  PROTEID. 


Casein. 


Glycocoll .0 

Alanin 0.9 

Lcucin 10.5 

Pyrrolidin  carbi).\\iic  acid.  3.1 

Phcnylalanin 3.2 

Glutamic  acid 10.7 

.•\spartic  acid 1.2 

Cystin 0.065 

Serin 0.23 

Oxy  a-pyrrolidin  carboxylic! 

acid '  0.25 

Tyrosin 4.5 

Aminovalcrianic  acid i.o 

Lysin ,  5.80 

Hislidin I  2.59 

Arginin I  4.84 

Tryptophan j  1.5 


Globin 

Gelatin. 

Elastin. 

FROM 

Hemo- 

16.5 
0.8 

globin. 

25-75 
0.58 

.0 
4-19     j 

2.1 

21.38 

29.04     j 

5-1 
0.4 
0.88 

1.74 

3-89 
0.76 

2-34     , 
4.24     1 

1-73 

0.56 

4-43 

.0 

1.0 

0.31 
0.56 

3-0 

1.04 

.0 

0-34 

^■53     i 

1.0 

1 

2-75 

4.28 

7.62 

10.90 

0.40 
.0 

0-3 

5-42 

*        1 

Edestin. 


3-8 
3-6 

20.9 

1-7 
2.4 

6.3 

4-5 
0.25 

0-33 


2.13 
* 

2.0 
1.0 
[I.7 


*  Present. 

Proteid  metaboHsm  in  plants  and  animals  occurs  in  striking 
similarity  to  the  changes  brought  about  by  enzymes  and  hy- 
drolytic  agents  acting  on  proteid  oustide  of  the  tissues.  Thus 
in  the  germinating  seed  Schultze^  finds  that  asparagin,  leucin, 
tyrosin,  histidin,  arginin  and  lysin  arise  from  the  metabolism 
of  proteid.  The  occurrence  of  leucin  and  tyrosin  in  the  Hver 
and  urine  in  such  a  diseased  condition  as  phosphorus-poisoning 
has  long  been  known,  and  Abderhalden  and  Bergell  ^  report  the 
presence  of  glycocoll  in  rabbit's  urine  after  the  administration  of 
phosphorus.  Urine  after  phosphorus-poisoning  may  also  con- 
tain phenylalanin  and  arginin.^  Wakeman  *  finds  an  altered 
quantitative  relationship  between  histidin,  arginin,  and  lysin 


'  Schultze  and  Castero:  "Zeitschr.  f.  physiol.  Chemie,"  1904,  Bd.  xliv,p.  455. 
'  Abderhalden  and  Bergell:  Ibid.,  1903,  Bd.  xxxix,  p.  464. 
'  Wolgemulh:  Ibid.,  1905,  Bd.  xliv,  p.  74. 
*  Wakeman:  Ibid.,    p.  333. 


THEORIES   OF   METABOLISM.  29I 

in  the  composition  of  liver  substance  after  phosphorus-poison- 
ing, arginin  in  particular  being  reduced  below  the  quantity  found 
in  the  liver  of  the  normal  dog.  This  possibly  suggests  a  ready 
destruction  of  certain  cell  proteids  rich  in  arginin  which  may  be 
essential  to  vitality. 

All  forms  of  proteid  decomposition  follow,  therefore,  the 
pathway  of  cleavage  into  amino  acids. 

The  life  history  of  many  of  these  substances  has  already 
been  set  forth  in  the  preceding  chapters,  and  it  is  here  un- 
necessary to  recapitulate. 

The  question  arises,  To  what  extent  may  the  amino  bodies 
formed  within  the  intestine  be  regenerated  into  proteid?  It  is 
beheved  that  the  cells  of  the  intestinal  villus  regenerate  fat  from 
fatty  acid  and  glycerin,  since  neutral  fat  alone  is  found  in  the 
thoracic  duct.  But  all  the  starch  fed  is  not  regenerated  into 
starch,  nor  is  maltose  regenerated  into  maltose  in  the  body. 
Much  may  be  burned  as  dextrose  and  only  a  part  is  transformed 
into  glycogen.  Long  ago  Schultzen  and  Nencki^  stated  that 
a  certain  amount  of  amino  bodies  formed  in  digestive  proteolysis 
was  absorbed  arid  burned,  and  that  the  absorbed  proteid  itself 
followed  the  lines  of  an  enzymotic  cleavage  into  amino  bodies. 
In  the  hght  of  newer  knowledge  several  authorities  have  recently 
elaborated  theories  along  similar  hnes.  It  has  been  pointed  out 
by  Folin^  that  there  is  Kttle  evidence  of  recontruction  of  all  the 
proteid  ingested.  He  cites  the  experiments  of  Nencki  and 
Zaleski,^'  which  showed  that  the  portal  blood  during  digestion 
contains  four  times  as  much  ammonia  as  arterial  blood,  and  that 
the  mucosa  of  both  stomach  and  intestine  yield  large  quantities 
of  ammonia.  The  inference  is  that  the  ammonia  of  the  portal 
vein  is  derived  from  ammonia  produced  in  the  mucosa  as  well  as 
from  that  which  normally  originates  in  the  intestine  during 
tryptic  proteolysis. 

1  Schultzen  and  Nencki:  "Zeitschrift  fiir  Biologic,"  1872,  Bd.  viii,  p.  124. 

2  Folin:  "American  Journal  of  Physiology,"  1905,  vol.  xiii,  p.  117. 

5  Nencki  and  Zaleski:  " Zeitschrift  fiir  physiologische  Chemie  "  1901,  Bd. 
xxxiii,  p.  206. 


292  SCIENCE   OF   NUTRITION. 

The  existence  of  denitrogenizing  enzymes  is  afforded  by  the 
example  of  the  guanase  and  adenase  of  Walter  Jones/  which 
respectively  convert  guanin  into  xanthin  and  adenin  into  hypo- 
xanthin  with  the  Uberation  of  ammonia. 

Folin  believes  that  the  greater  part  of  the  proteid  ingested 
undergoes  a  dcnitrogenization  through  the  hydrolysis  of  the 
amino  cleavage  products.     Such  a  reaction  would  read 

^  CNHj  +  H2O  =  ^  COH  +  NH3 

The  ammonia  may  be  converted  into  urea  within  the  organism, 
and  the  nitrogen-free  rest  may  be  converted  into  sugar.  The 
simplest  expression  of  this  is  seen  in  the  experiment  of  Neuberg 
and  Langstein,^  who  found  glycogen  in  the  liver  and  lactic  acid 
in  the  urine  of  a  rabbit  following  the  ingestion  of  alanin.  The 
transformation  of  alanin  into  lactic  acid  may  be  written 

CH3  CHNH2  COOH  +  HjO  =  CH3  CHOH  COOH  +  NH3 
Alanin.  Lactic  Acid. 

The  conversion  of  lactic  acid  into  sugar  was  demonstrated 
by  the  experiment  of  Embden  and  of  A.  R.  Mandel,  who  showed 
increases  in  the  sugar  output  in  diabetes  after  the  ingestion  of 
lactic  acid. 

Wolf^  finds  that  none  of  these  amino  substances  has  any 
effect  on  the  blood  pressure  of  animals  so  far  as  he  has  examined 
them.  Abderhalden  and  Teruuchi  *  find  that  their  nitrogen  is  in 
greater  part  converted  into  urea  in  the  organism  as  well  as  that 
of  artificially  prepared  peptids,  such  as  glycyl-glycin. 

Although  some  proteid  metabolism  may  take  place  as  above 
outlined,  it  is  an  undoubted  fact  that  proteid  may  be  synthesized 
in  the  body  with  the  formation  of  new  tissue,  and  also  that  pro- 
teids  injected  into  the  blood  stream,  as  in  cases  of  transfusion 

'  Jones  and  Winternitz:  "Zeitschrift  f  iir  physiol.  Chemie,"  1905,  Bd.  xliv,  p.  i. 
^Neuberg  and  Langstein:  "Archiv  fur  Physiologic,"  Suppl.   Bd.,    1903, 
p.  514- 

'  Wolf:  "Journal  of  Physiology,"  1Q05,  vol.  xxxii,  p.  171. 

*  Abderhalden  and  Teruuchi:  "Zeitschrift  flir  physiologische  Chemie," 
1906,  Bd.  xlvii,  p.  159. 


THEORIES   OF   METABOLISM.  293 

of  blood  serum,  are  rapidly  destroyed  and  the  nitrogen  elimi- 
nated as  urea.  The  conditions  of  proteid  metabolism  may, 
therefore,  be  entirely  similar  to  those  of  starch  metabolism: 
(i)  digestive  hydrolysis;  (2)  partial  combustion  of  the  end 
products;  and  (3)  possible  regeneration  of  portions  of  the  end 
products  into  substances  similar  to  the  originals,  but  characteris- 
tic of  the  organism, — i.  e.,  glycogen  and  body  proteids.  In  the 
case  of  proteids  the  second  or  metabolic  process  involves  the 
partial  passage  of  the  end  products  through  the  glucose  stage. 
The  third  or  regenerative  process  is  promoted  by  such  a  proteid 
as  casein,  vv^hich  yields  a  large  variety  of  cleavage  products. 

The  chemical  bases  of  such  reconstruction  is  afforded  by 
the  artificial  production  of  peptids  by  Emil  Fischer,  bodies  which 
contain  two  or  more  amino  acids  united  together.  There  are 
di,-  tri,-  and  poly-peptids.  For  example,  glycyl-glycin  is  formed 
by  the  union  of  two  molecules  of  glycocoll  with  the  loss  of  one 
of  water,  as  follows : 

NH2CH2CO  OH  +  HNHCH2COOH  — H2  0  = 
Glycocoll.  Glycocoll. 

NH2  CH2  CO  NHCHj  COOH 

Glycyl-glycin. 

Kindred  substances  are  alanyl-alanin,  alanyl-glycin,  leucyl- 
glycyl-glycin,  dialanyl-cystin.^  Their  fate  in  metabohsm  is  the 
same  as  that  of  proteid,  and  it  is  claimed  that  the  presence  of 
some  of  them  is  necessary  for  the  proper  s}Tithesis  of  proteid  in 
the  organism  (p.  105). 

FoHn^  has  discovered  that  a  man  fed  with  creatin-free  food 
eliminates  a  constant  quantity  of  creatinin  nitrogen  in  the  urine 
irrespective  of  the  amount  of  nitrogen  ingested  with  the  food. 
Thus  the  urine  of  one  man  contained  16.8  grams  of  total  ni- 
trogen with  0.58  gram  of  creatinin  nitrogen.  The  same  man  at 
another  time,  after  large  carbohydrate  ingestion,  eliminated  3.60 
grams  of  total  nitrogen  and  0.60  gram  of  creatinin  nitrogen. 
Folin  conceives  that  the  constancy  of  the  creatinin  and  uric  acid 

*  Consult  Abderbalden:  "Lehrbuch  der  physiologischen  Chemie,"  1906. 
'  Folin:  "American  Journal  of  Physiology,"  1905,  vol.  xiii,  p.  66. 


294  SCIENCE    OF   NUTRITION. 

output  is  a  true  index  to  the  necessary  protoplasmic  breakdown, 
and  would  define  the  nitrogen  of  such  destruction  as  the  endog- 
enous nitrogen.  To  what  extent,  if  any,  urea  nitrogen  enters 
into  this  essential  life  metabolism  he  is  not  prepared  to  say. 
The  same  idea  was  expressed  by  Burian'  in  an  article  published 
ten  days  later  than  FoUn's.  Burian  beUeves  that  purin  bases 
are  a  constant  product  of  muscle  metabolism  and  that  these 
are  oxidized  to  uric  acid,  a  part  of  which  is  further  converted  into 
urea.  This  process  of  itself  would  indirectly  evolve  urea  as  a 
constant  product  of  the  endogenous  nitrogen  metabolism.  Ac- 
cording to  this  newer  conception  the  cells  of  the  body  through 
the  swinging  motion  of  their  particles  do  continually  break  down 
their  own  protoplasm  with  the  production  of  creatinin,  purin 
bases,  and  perhaps  other  substances.  These  same  cells  may 
also  break  up  exogenous  amino  radicles  derived  from  ingested 
proteid  or  circulating  proteid  itself. 

As  regards  fat  metabolism  Geelmuyden^  is  inchned  to  the 
opinion  that  oxybutyric  acid,  aceto-acetic  acid  and  acetone  are 
normal  metabolism  products  derived  from  members  higher  up 
in  the  series. 

Stoklasa^  finds  a  ferment  in  animal  tissues  able  to  convert 
sugar  into  lactic  acid.  He  quotes  Oppenheimer's  experiment, 
showing  that  whereas  fresh  normal  blood  yielded  little  acid  on 
standing  at  37°,  much  greater  amounts  were  formed  if  dextrose 
were  added.  He  believes  that  this  lactic  acid  is  subsequently 
converted  into  alcohol  and  carbon  dioxid.  He*  describes  the 
action  of  ferments  as  follows :  Lactalase  converts  dextrose  into 
lactic  acid;  alcoholase  converts  lactic  acid  into  alcohol;  aceto- 
lase  converts  alcohol  into  acetic  acid:  and,  perhaps,  formilase  con- 
v-erts  acetic  into  the  unstable  formic  acid  which  yields  methane. 

Rubner^  gives  the  following  theory  of  metabohsm:    Living 

'  Burian:  "Zcitschrift  fiir  physiologische  Chemie,"  1905,  Bd.  xliii,  p.  532. 

-  Geelmuyden :  Ibid.,  1904,  Bd.  xli,  p.  12S. 

^  Stoklasa,  Jelinck  and  Czerny :  "Centralblatt  fur  Physiologic,"  1903,  Bd.  xvi, 
p.  712. 

*  Stoklasa:  Ibid.,  1905,  Bd.  xviii,  p.  793. 

*  Rubner:  Von  Leyden's  "  Handbuch  der  Ernahrungstherapie, "  1903,  p.  78. 


THEORIES    OF    METABOLISM.  295 

protoplasm,  through  the  vibration  of  its  particles,  metabolizes  the 
food  substances.  The  action  resembles  catalysis.  The  energy 
Liberated  reacts  on  the  particles  of  protoplasm,  causing  a  change 
in  their  position  and  a  cessation  of  metabohsm.  The  particles 
then  return  to  their  original  position  and  the  cycle  begins  again. 
These  processes  require  a  fixed  amount  of  energy.  Rubner  does 
not  give  his  reasons  for  beheving  in  this  rhythm  of  excitation  and 
rest. 

The  quantity  of  the  combustion  depends  on  the  power  of  the 
cells  to  metaboHze  (Voit).  In  the  resting  state  this  metaboUc 
power  of  the  cells  is  influenced  by  the  "law  of  skin  area"  (Rub- 
ner). Temperature  (cooling  or  warming)  and  nerve  excitation 
(muscle  work,  chemical  regulation)  affect  the  power  of  the  cells 
to  metaboKze,  perhaps  through  a  variation  in  the  capabihty  of 
oscillation  of  the  particles,  an  effect  which  is  in  turn  maintained 
at  the  expense  of  the  energy  derived  from  metabolism.  Living 
protoplasm  metabolizes  in  accord  with  its  necessities  at  the  time, 
and  never  more.  Large  quantities  of  nutrient  materials  fur- 
nished will  not  increase  cell  metabolism.  If  food  be  ingested 
above  the  requirement  for  the  organism,  any  excess  will  be 
retained  in  the  body.  The  kind  of  metabohsm  depends  upon 
the  constitution  of  the  fluid  feeding  the  cells,  whether  proteid, 
carbohydrates  or  fats  have  been  ingested. 

Each  ingested  foodstuff  exerts  a  specific  dynamic  action 
(Rubner).  At  a  temperature  of  33°  the  ingestion  of  the  starva- 
tion requirement  of  energy  in  the  form  of  fat  increases  the  re- 
qirement  for  energy  10  per  cent.,  carbohydrate  raises  it  5  per 
cent.,  proteid  30  per  cent.  In  other  words,  in  the  case  of  meat, 
in  order  to  obtain  calorific  equilibrium  about  140  calories  must 
be  ingested  instead  of  100,  if  that  represents  the  starvation  re- 
quirement. Rubner^  explains  that  the  cells  of  the  body  do  not 
require  more  energy  after  meat  ingestion  than  in  starvation, 
but  that  the  heat  produced  by  a  prehminary  cleavage  of  proteid 
into  dextrose  on  the  one  hand,  and  into  a  nitrogen-containing  rest 
on  the  other,  while  yielding  heat  to  the  body  does  not  furnish  the 
^  Rubner:  "Gesetze  des  Energieverbrauchs,"  1902,  p.  380. 


296  SCIENCE   OF   NUTRITION. 

actual  energy  for  the  vital  activities  of  the  protoplasm.  This 
is  furnished  principally  by  the  dextrose  derived  from  the  proteid. 
Although  it  is  necessary  to  abandon  the  older  theory  which 
pronounces  glycogen  (or  dextrose)  a  direct  cleavage  product  of 
proteid,  still  the  explanation  of  Rubner  remains  tenable  if  inter- 
preted in  a  newer  light.  If  the  energy  requirement  of  the 
cell  remains  constant  at  100,  even  after  the  ingestion  of  140 
calories  of  proteid,  then  71.4  per  cent,  of  the  total  heat  value  of 
the  proteid  is  the  quantity  actually  used  for  the  vital  processes. 
Since  it  has  been  shown  in  the  writer's  laboratory  that  meat 
proteid  yields  58  per  cent,  of  dextrose  in  metabolism,  it  may  be 
calculated  that  52.5  per  cent,  of  the  total  energy  of  proteid  may  be 
available  for  the  cells  in  the  form  of  sugar.  A  balance  of  19 
per  cent,  must  be  obtained  from  other  compounds,  while  28.5 
per  cent,  of  the  total  heat  value  is  wasted  as  heat  without  ever 
having  been  brought  into  the  service  of  the  life  processes  of  the 
cells.  Perhaps  this  28.5  per  cent,  of  heat  loss  represents  the 
quantity  produced  by  the  cleavage  of  proteid  into  amino  bodies 
and  the  denitrogenization  of  these  radicles.      (See  p.  140.) 

The  constancy  of  the  energy  requirement  in  metabolism 
makes  difficult  the  explanation  of  the  action  of  the  various  fer- 
ments found  in  the  body.  These  are  of  three  varieties :  hydro- 
lytic,  synthetic,  and  oxidizing,  but  these  from  the  very  principles 
of  our  knowledge  must  be  subservient  to  the  requirement  of  the 
living  cells,  and  not  themselves  masters  of  the  situation,  as, 
for  example,  they  become  in  the  autolysis  of  dead  tissue.  It 
seems  to  be  the  requirement  of  the  mechanism  of  cell  activity 
which  determines  metaboHsm,  and  not  primarily  the  action  of 
enzymes,  whose  influence   appears   to  be  only  intermediary. 

Friedenthal*  shows  that  proteid,  colloidal  carbohydrates, 
fats  and  soaps  are  not  oxidizable  in  the  cellular  fluids  without 
previous  hydrolytic  cleavage.  After  hydrolysis,  however,  the 
oxidases  may  effect  an  oxidation  of  the  smaller  molecules.  The 
necessity  of  the  hydrolytic   ferment  is  also  seen  in   the   non- 

*  Friedenthal:  Verhandlungen  der  Berliner  Physiologischen  Gesellschait, 
"Archiv  fiir  Physiologic,"  1904,  p.  371. 


THEORIES   OF  METABOLISM.  297 

combustion  of  dextrose  after  the  extirpation  of  the  pancreas,  the 
organ  by  which  the  ferment  is  supphed.  Oxygen  and  the 
oxidases  are  present  in  ample  quantity,  but  the  sugar  is  not 
burned  unless  it  be  broken  by  its  specific  ferment.  In  the  mean- 
time the  cell  avails  itself  of  a  compensatory  energy  supply  from 
other  sources.  It  is  impossible  to  apply  anything  similar  to 
Ehrlich's  side-chain  theory  to  this  condition  of  affairs,  for  the 
metabolism  does  not  depend  upon  the  satisfaction  of  chemical 
affinities,  but  rather  upon  a  definite  law  of  utilization  of  energy 
equivalents. 

However  clearly  formulated  the  laws  of  metabohsm  may  be, 
and  many  of  them  are  as  fixed  and  definite  as  are  any  laws  of 
physics  and  chemistry,  still  the  primary  cause  of  metabolism 
remains  a  hidden  secret  of  the  living  bioplasm. 


APPENDIX. 


TABLE  SHOWING  THE  COST  OF  PROTEID  AND  ENERGY 

As  Furnished  by  a  NuiiBER  of  Common  Food  Materials,  at  Prices  Current  in   the 
Eastern  Part  of  the  United  States. 

Compiled  by  Langworthy,  U.  S.  Department  of  Agriculture,  1905,  in  Farmers'  Bulletin, 

No.  85,  p.  19. 

(i  pound  :=  453-6  grams.) 


Kind  of  Food  Material. 


Oh  a 

H  3 


Cents. 

Codfish,  whole,  fresh 10 

Codfish,  steaks 12 

Bluefish 12 

Hahbut 18 

Codfish,  saU 7 

A'lackeral,  saU 10 

Salmon,  canned 12 

Oysters  (solids,  30  cents  quart).. |  15 

Oysters  (solids,  60  cents  quart) . .  30 

Lobster 18 

Beef,  sirloin  steak 25 

Beef,  sirloin  steak 20 

Beef,  round 14 

Beef,  stew  meat 5 

Beef,  dried,  chipped 25 

Mutton  chops,  loin 20 

Mutton,  leg 22 

Pork,  roast,  loin 12 

Pork,  smoked  ham !  22 

Milk  (7  cents  quart) 3 

Milk  (6  cents  quart) 3 

Wheat  flour 3 

Corn  meal 2 

Potatoes  (90  cents  bushel) i  J 

Potatoes  (45  cents  bushel) f 

Cabbage 2^ 

Corn,  canned 10 

Apples I J 

Bananas 7 

Strawberries 7 


Dollars 
0.90 

71 
1.20 
i.iS 

■44 
.61 
.62 

2.50 
5.00 

3-05 

1.52 

1. 21 

•74 

■38 

•95 
1.48 
1.46 

.90 

^•55 

1.06 

.91 

.26 

•83 

.42 

1.79 

3^57 
5.00 

8.75 
7.78 


O   w 


Cents. 
48 
36 
58 
40 

23 

10 

18 

68 

136 

129 

26 

21 

16 

5 

33 

14 

25 

10 

14 


Amounts  for  10  Cents. 


a 

<  &  < 


Lbs. 


23 

7 

24 

42 


833 
833 
556 
429 
000 

833 
667 

333 
556 
400 
500 

714 
000 
400 
500 
454 
833 
454 
857 
333 
333 
000 
667 

333 
000 

GOD 
667 
429 
429 


Lb. 
o.iri 
.142 
.083 
•085 
.229 
.163 
.162 
.040 
.020 

•033 
.066 
.083 
.136 
.266 
.106 
.068 
.069 
.112 
.064 
.094 
.110 
.380 
.460 
.120 
.240 
.056 
.028 
.020 
.011 
.013 


Calories. 
209 
274 
172 
253 
437 
998 

547 

147 

74 

77 

380 

475 

615 

1,862 

303 
694 

394 

1,016 

729 

891 

1,040 

5,363 

8,05s 

2,020 

4,040 

484 

444 

1,420 

414 

240 


299 


300 


SCIENCE   OF   NUTRITION. 


A  more  extensive  compilation  which  permits  not  only 
the  calculation  of  the  nutritive  value  of  the  particular  edible 
food  but  also  of  the  approximate  weight  of  inedible  waste  en- 
tailed in  the  direct  purchase  of  the  material  in  the  market, 
is  as  follows : 


COMPOSITION   OF   ORDINARY   FOOD   MATERIALS      • 
According  to  Atwater  and  Bryant. 
Report  of  the  Storrs  Agricultural  Experiment  Station,  1899,  p.  113,  somewhat  abridged. 


Kind  of  Food  Material. 


Animal  Foods. 
Beej  (fresh). 

Brisket 

Chuck 

Flank 

Loin,  lean 

Loin,  medium , 

Loin,  fat 

Neck 

Plate 

Ribs 

Round,  lean 

Round,  medium 

Round,  fat 

Round,  second  cut 

Rump 

Fore  shank 

Tongue 

Shoulder  and  clod 

Fore  quarter 

Hind  quarter 

Side,  lean 

Side,  medium 

Side,  fat 

Liver 

Suet  (unrendercd  tallow). 
Hind  Shank 


Beef    (preserved   and 
cooked). 

Dried  and  smoked 

Brisket,  corned 

Flank,  corned 


% 

23-3 
16.3 
10.2 
131 
^3-3 
10.2 
27.6 
16.5 
20.8 
8.1 
7.2 
12.0 

19-5 

20.7 

36.9 
26.5 
16.4 

18.7 
15-7 
19-5 
17.4 
13.2 


53-9 


Edible  Portion. 


% 

54 
62 
60 
67 
60 
54 

63 

54 
55 
70 

65 
60 

69 

I  56 

67 

70 

68 
160 

'59 
67 

59 
47 


13-7 
67.8 


4-7  54-3 
21.4  50.9 
12. 1    I  49.9 


<2  3 


% 


Available  Nutrients. 


% 

15-3 
17.9 
18.3 
19.1 
17.9 
17.0 

19-5 
16.0 
17.0 
20.7 
19.7 
18.9 
19.8 
16.9 
19.8 
18.3 
19.0 
17.4 
17.8 
18.7 
17.6 

15-7 

20.4 

4.6 

20.3 


3-5  29.1 
3-2  [17-8 
2.7  I  14.2 


% 
27.1 
17.1 
19.9 
12. 1 
19.2 
26.2 

15-7 
27.6 

25-3 

7-5 

12.9 

18.5 

8.2 

24.2 

II.O 

8.7 
10.7 
20.3 
20.5 

12.5 
20.9 
34-6 
4-3 
77-7 
10.9 


6.2 
23-5 
31-4 


o  « 


% 


% 

7 
7 
7 


6.8 
4.2 
2.2 


■5=9 -^E 


Calo- 
ries. 

1475 
1095 
1225 
900 
1185 
1470 
1065 
1510 
1430 

735 
950 

"75 
750 

1380 
865 
740 
840 

1220 

1240 
910 

1250 

1805 
620 

3440 
875 


850 
1370 
1635 


APPENDIX. 


301 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


PL,      . 


Edible  Portion. 


Animal  Foods. 

{Beef,  preserved  and 

cooked). 

Plate,  corned 14.5 

Rump,  corned 6.0 

Canned,  boiled 

Canned,  corned 

Boiled  beef  (cut  not  given) 

Roast,  cooked - 

Loin  steak,  cooked 

Tripe,  pickled 


Veal  {fresh). 

Breast 

Chuck 18.9 

Cutlets  (round) j    3.4 

Flank '     .. 

Leg 

Loin 

Neck 

Rib 

Shank ;  62.7 

Fore  quarter 24.5 


21-3 


14.2 
16.5 
31-5 
24-3 


Hind  quarter. 

Side 

Liver 


Lamb  {fresh). 

Breast  or  chuck 

Leg 

Loin 

Neck 

Shoulder 

Fore  quarter 

Hind  quarter 

Side 


20.7 
22.6 


19. 1 
17.4 
14.8 
17.7 
20.3 
18.8 
iS-7 
19-3 


Lamb  {cooked). 

Chops,  broiled '  13.5 

Leg,  roast 

Mutton  {fresh). 

Chuck 21.3 

Flank I    9.9 


40.1 
58.1 
51-8 
51.8 
38.1 
48.2 
54-8 
86.5 


66.0 

73 -o 
70.7 
68.9 
70.0 
69.0 
72.6 
72.7 

74-5 
71.7 
70.9 
71-3 
73-0 


56.2 
63-9 
53-1 
56-7 
51.8 

55-1 
60.9 
58.2 


47.6 
67.1 


50-9 
46.2 


Available  Nutrients. 


% 


3-7 
2.2 
2.2 

2-7 

2.7 

2.4 

2.0 

.6 


1-3 
1-3 
1-3 
1-3 
I.I 
1.2 
i.o 
1.2 
1.2 
1.2 
•9 


2.0 

1-7 
2.2 
1.9 
2.2 
2.0 
1.8 
2.0 


2-5 

1.4 


2.4 
2.6 


% 


13-3 
14.8 
24.7 
25-5 
25-4 
21.6 
22.8 
"•3 


% 


39-S 
22.1 
21.4 
17.8 

33-2 
27.2 
19.4 


18.9 

13-3 

I9.I 

t>.2 

19.7 

7-3 

19-9 

9-9 

19.6 

8.6 

19-3 

10.3 

19.7 

6.6 

20.1 

5-8 

20.1 

4.4 

19.4 

7.6 

20.1 

7-9 

19.6 

7-7 

9-7 

S-o 

18.5 

18.6 
I8.I 

17.2 

17.6 

17.8 

19.0 

17. 1 


21.0 

I9.I 


14.6  31.9 

14.7  36.4 


22.4 

15-7 
26.9 
23.6 
28.2 

24-5 
18.1 
21.9 


28.4 


% 


i>t;  !?g 

i"?  ft  II  o 


%     1    Calo- 
ries. 


3-S 
2.8 
1.0 
3-0 

•7 
1.0 

•9 


1980 
125b 
1415 
127s 
1930 
1410 
1290 
275 


950 
650 
710 
825 
760 
830 
680 
650 
590 
715 
740 

725 
410 


.8 

1335 

.8 

1050 

.8 

1520 

.8 

1360 

.8 

1565 

.8 

1410 

.8 

1160 

.8 

1285 

[.0 

1640 

.6 

905 

•7 

i66s 

•5 

i860 

302 


SCIENCE   OF   NUTRITION. 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


Animal  Foods. 

Mutton  (Jresh) 

Leg 

Loin 

Neck 

Shoulder 

Fore  quarter 

Hind  (|uartLr 

Side 


Mutton  {cooked  arid 
canned). 

I>cg,  roast 

Corned,  canned 

Tongue,  canned 


Pork  {fresh). 
Chuck,  ribs  and  shoulder. 

Flank 

Loin,  chops 

Ham 

Shoulder 

Side 


Pork  {pickled,  salted  and 
smoked). 

Bacon 

Ham 

Shoulder 

Salt,  lean  ends 

Salt,  fat 

Pigs'  feet,  pickled 

Pork  {cooked). 

Ribs,  cooked 

Steak,  cooked 


Sausage. 

Bologna 

Frankfort 

Pork 


p5t3 


% 

18.4 
16.0 
27.4 
22.5 
21.2 
17.2 
18.I 


Edible  Portion. 


18.0 
19.7 
10.7 
12.4 
II-5 


7-7 
13.6 
18.2 


35-5 


Poultry  and  game  {jresh). 

Chicken,  broilers 

Fowl 

Goose 

Turkey 


Available  Nutrients. 


3-3 


41.6 

25-9 
17.6 
22.7 


% 
62.8 
50.2 
58.1 
61.9 

52-9 
54-8 
54-2 


50.9 
45-8 
47.6 


59-0 
52.0 

53-9 
51-2 
34-4 


40.3 
45 -o 
19.9 

7-9 
68.2 


33-6 
33-2 


60.0 

57-2 
39-8 


I74.8 

637 
46.7 

55-5 


% 

1-7 
2.4 
2.0 

1-7 
2.2 
2.1 
2.1 


2.1 
3-0 
3-1 


2-3 

1.9 
2.2 
2.1 

2-3 

3-2 


4.8 

3-6 
3-8 
5-1 
5-4 
1.4 


3-1 
3-3 


2.4 

2-3 

3-1 


i.o 
1.6 

2-5 

1.9 


% 

17.9 

1-55 
16.4 
17.2 

iS-i 
16.2 

15.8 


24-3 
27.9 

23-7 


16.8 
17.9 
16.1 
14.8 
12.9 


9.6 
15-8 
15-4 


15.8 


24.1 
19-3 


19.0 
12.6 


20.9 
18.7 
15.8 
20.5 


% 
17. 1 
31-4 
23-4 
18.9 
29.4 
26.7 
27-S 


21.5 
21.7 
22.8 


29-5 
21. 1 
28.6 
27-5 
32-5 
52-5 


64.0 
36.9 
30-9 
63-7 
81.9 
14.1 


35-7 


% 


16.7 

0-3 

17.7 

I.I 

42.0 

I.I 

2.4 

15-5 

34-4 

21.8 

% 


•9 
3-2 
3-6 


3-3 
3-6 
5-0 
4-3 
2.9 

•7 


1-7 
I.I 


2.8 
2.6 
1-7 


"=■110 


Calo- 
ries. 

1095 
1 660 

1335 
1 160 

1570 
1475 
1500 


1410 
1495 
1045 


1605 
1265 

1555 
1480 
1660 
2440 


2950 

1905 
1640 
2905 

3565 
920 


2020 
2245 


1085 
1160 
2080 


520 
.8  I  1040 
.6   1800 

.8  I  853 


APPENDIX. 


303 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


Shell  fish  {jresJi). 
Long  clams,  in  sheU... 
Round  clams,  in  shell. 

Oysters,  in  shell 

Oysters,  solids 

Clams,  round,  solids.. 

Crabs,  hard  shells 

Lobster 


Animal  Foods. 

Poultry  and  game  {cooked 

and  canned). 

Capon 

Turkey,  roast 

Plover,  roast,  canned 

Quail,  canned 


Fish  {fresh). 
Bass,  black,  whole. 

Bluefish  

Codfish,  dressed  . . 

Cod  steaks 

Flounder,  whole. . . 

Haddock 

Halibut  steak 

Lake  trout 

Mackerel 

Weakfish 

Whitefish,  whole... 


Edible  Portion. 


% 


10.4 


S4.8 
48.6 
29.9 
9.2 
61.5 
51.0 
17.7 
48.5 
44-7 
51-9 
53-5 


41.9 

67-5 
81.4 


52-4 
61.7 


24.9 
1.6 
7.0 


Fish  {preserved  and 
canned). 

Cod,  salt 

Cod,  salt,  boneless. . . . 

Halibut,  smoked 

Herring,  smoked '  44.4 

Mackeral,  salt,  dressed...'  19.7 

Salmon,  canned 14.2 

Sardines,  canned 5.0 

Lobster,  canned 

Clams,  canned 

Oysters,  canned 


% 


59-9 
67-5 
57-7 


76.7 
78.S 
58.5 
79-7 
84.2 
81.7 

75-4 
70.8 

73-4 
79.0 
69.8 


85.8 
86.2 
86.9 
88.3 
80.8 
77.1 
79.2 


53-5 
55-0 
49.4 
34-6 
43-4 
63-5 
52-3 
77.8 
82.9 
83-4 


>  3 


% 


1-7 
1-3 
1-7 
1.6 


i.o 

i.o 

•S 

•9 

•7 


1.0 

•9 
.8 
.6 

1.0 
1.4 


6.8 
5-5 
5-0 
5-2 
5-0 
1.9 

3-1 
1-3 
1.0 


Available  Ndtrients. 


% 


26.2 
17.1 

21.7 


10.8 
18.1 
13.8 
16.7 
18.0 

17-3 
18.1 

17-3 
22.2 


8.3 
6.3 
6.0 

5-8 
10.3 
16.1 
15-9 


20.9 
24.9 
20.1 
35-8 
16.8 
21. 1 
22.3 
17.6 
10.2 
8.5 


% 


10.9 
10.9 

9-7 
7.6 


1.6 

I.I 

.2 

•5 
.6 

•3 
4.9 
9.8 
6.7 

2-3 

6.2 


•4 
I.I 
1.2 
1.0 
1.9 
1-7 


•3 

•3 

14-3 

15.0 

25.1 

18.7 

1.0 

.8 

2-3 


00 


% 


1.6 
I.I 


2.0 
4.2 
3-7 

5-2 
1.2 

•4 


% 


1.0 
2.4 
7.6 
^•7 


2.0 
2.0 

1-5 
.8 

1-7 

2-3 

1-7 


18.5 

14-3 

II-3 

9.9 

9-7 
2.0 
4.2 
1.9 


3lt2  "5 


Calo- 
ries. 


995 
855 
985 
780 


470 
420 
225 

385 
300 

345 
570 
765 
650 

445 
710 


240 
215 
235 
225 

340 
425 
400 


430 

510 

1015 

1360 

1415 

915 

1250 

400 

290 

340 


304 


SCIENCE   OF   NUTRITION. 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


Animal  Foods. 

Eggs,  uncooked 

Eggs,  boiled 

Dairy  products,  etc. 

Whole  milk 

Skim  milk 

Condensed     milk,    sweet- 
ened  

Cream 

Cheese 

Butter 

Oleomargarine,  etc , 

Lard,  cottolene,  etc 

Animal  Food. 

Miscellaneous. 

Gelatin 

Calf 's-foot  jelly 

Vegetable  Foods. 
Cereals,  etc. 

Barley,  pearled 

Buckwheat  flour 

Buckwheat,  self-raising... 

Corn  (maize)  flour. 

Corn  (maize)  meal 

Corn  (maize)  preparations 

CereaHnc 

Hominy 

Hominy,  cooked 

Oatmeal  and  rolled  oats. . 

Oatmeal,  boiled 

Rice 

Rice,  boiled 

Rye  flour 

Entire  wheat  flour 

Gluten  flour 

Graham  flour 

Wheat  flour,  patent  proc- 
ess: 

Low  grade 

Baker's  grade 


3 

Edible  Portion. 

Available  Nutrients 

!!?« 

•HS 

<u  „• 

<u 

11 

•6 

II 

1  Value 
erlb. 
4S3-6 
rams. 

1 

1 

5^ 

0 
u 

^ 

.^ 

< 

3  o-llO 

% 

% 

% 

% 

% 

% 

% 

Calo- 
ries. 

II. 2 

7.3-7 

I.I 

13.0 

lO.O 

.8 

69s 

II. 2 

73-2 

1.2 

12.8 

11.4 

.6 

755 

87.0 

•s 

3-2 

3-8 

5-0 

•5 

310 

90-5 

•3 

3-3 

•3 

5-1 

•5 

170 

26.9 

1.2 

8-.S 

7-9 

54-1 

1.4 

1460 

74.0 

I.I 

2.4 

17.6 

4-5 

•4 

860 

34-2 

3-4 

251 

32.0 

2.4 

2.9 

1885 

II.O 

4-9 

I.O 

80.8 

2-3 

3410 

9-5 

5-7 
5-0 

1.2 

78.9 
95-0 

4-7 

3335 
3985 

13.6 

3-2 

88.7 

.1 

1.6 

2125 

77.6 

•3 

4.2 

17.4 

•5 

410 

"•,■; 

4.0 

6.6 

1.0 

76.1 

.8 

1630 

13.6 

3-5 

5-2 

I.I 

75-9 

•7 

1600 

11.6 

4.9 

6.7 

I.I 

71-5 

4.2 

1545 

12.6 

3-6 

S« 

1.2 

76.3 

■S 

1625 

12.S 

4.0 

7-5 

1-7 

73-5 

.8 

1625 

IO-3 

4.2 

7.8 

1.0 

76.3 

•4 

1655 

11.8 

3-« 

6.8 

•5 

76.9 

.2 

1625 

79-3 

•9 

1.8 

.2 

17.4 

■4 

375 

7.8 

5-6 

13-4 

6.6 

65.2 

1.4 

1795 

•«4-5 

•9 

2-3 

•5 

"•3 

-.=; 

285 

12.3 

3-7 

0-5 

•3 

76.9 

•3 

1610 

72.5 

I.I 

2-3 

.1 

23.8 

.2 

50s 

12.9 

Z-b 

5-3 

.8 

76.9 

•s 

1610 

11.4 

4-5 

10.7 

1-7 

70.9 

.8 

164s 

12.0 

4.6 

II.O 

1.6 

70.1 

•7 

1630 

II-3 

4-7 

10.3 

2.0 

70.4 

1-3 

1640 

12.0 

4-5 

10.9 

1-7 

70.2 

•7 

1635 

11.9 

4.2 

10.3 

1.4 

71.7 

•5 

1640 

APPENDIX. 


305 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


Vegetable  Foods. 
Cereals,  etc. 

Family    and    straight 
grade 

High  grade 

Wheat  preparations: 

Breakfast  foods 

Macaroni 

Macaroni,  cooked  .. . . 

Spaghetti 

Noodles 

Bread: 

Brown 

Corn  (johnnvcake) 

Rye..'. ' 

Graham 

Whole  wheat 

White  wheat 

Biscuit,  soda* 

Rolls 

Toasted  bread 

Crackers: 

Boston  (split) 

Milk,  cream 

Graham 

Oyster 

Soda 

Water 

Cakes,  cookies,  etc.: 

Bakers'  cake 

Coffee  cake 

Gingerbread 

Sponge  cake 

Drop  cake 

Molasses  cookies 

Sugar  cookies 

Ginger  snaps 

Wafers 

Doughnuts 

Pie,  pudding,  etc.: 

Pie,  apple 

Pie,  custard 

Pie,  squash 


|3 


% 


Edible  Portion. 


% 

12.8 
12.4 

9.6 
10.3 
78.4 
10.6 
10.7 

43-6 
38.9 
35-7 
35-7 
38.4 
35-3 
22.9 
29.2 
24.0 

7-S 
6.8 

S-4 
4.8 

5-9 
6.8 

31-4 
21.3 
18.8 

15-3 
16.6 
6.2 
8.3 
6.3 
6.6 
18.3 

42-5 
62.4 
64.2 


% 


4.0 
4.0 

4-5 
4-5 
1-3 
4.0 
4.2 

2.8 
3-5 
3-4 
3-4 
3-2 
?,■?, 
4-7 
3-6 
4.1 

5-0 
5-0 
4.8 

5-4 
4.9 

S-o 

Z-i 
3-8 

4-3 

4.4 

4-5 
4-7 
4-5 
4-7 
4.8 
4.8 

3-1 
2.2 
2.4 


Available  Nutrients. 


% 


8.3 
8.7 

9-3 
10.4 

2-3 

9.4 
9.1 

4.2 
6.5 
7-3 
6.9 

7-S 
7-1 
7.2 
6.9 
8.9 

8.5 
7-5 
7-7 
8.8 
7.6 
8.3 

4.8 
5-5 
4-5 
4.8 

5-9 
5-6 
5-4 
5-0 
6.7 

5-2 
2.4 

3-2 

3-4 


% 


i.o 
■9 


•5 
1.6 

.8 

1.2 

12.3 

3-7 

1-4 

7-7 
10.9 

8.5- 
9-S 

8.2 

7-9 

4.1 
6.8 
8.1 
9.6 

13.2 
7.8 
9.2 
7-7 
7-7 

18.9 


5-7 
7.6 


% 


73-5 
73-6 


% 


52.0 

51-3 
49.1 

52-3 
51.8 

55-8 
60.3 

69.9 
68.5 
72-5 
69-3 
71.8 
70.6 

55-8 
61.9 
62.1 
64-5 
59-2 
74.0 
71.6 
74-3 
73-0 
52-1 

41.8 

257 
21.4 


—  u  ^2 

3  a  II  O 


Calo- 
ries. 


1.6 

74.0 

1.0  : 

.8 

73-0 

1.0 

1-4 

iS-6 

1.0 

•4 

75-1 

■5 

•9 

74.3 

•8  , 

1.6 

46.2 

1.6 

4.2 

45-2 

1-7 

■4      1615 
.4      1620 


1670 
1640 

405 
1640 
1640 

1035 
1 1 70 
1 1 60 
1185 
1125 
"95 
1655 
1360 
1390 

1830 
1920 
1900 

1905 
1870 
1850 

1335 
1580 
1620 

1735 
180  ■; 

1855 
1865 

1845 
1855 
1895 

1215 

795 
800 


I.I 
I.I 
1.0 


1-3 

1.4 

1-3 
I.I 
2.2 
1.6 
1.4 

.6 

•7 
2.2 
1.4 

.6 

1-7 
1.0 
2.0 
1.2 
•7 

1.4 
.8 


*  Made  from  wheat  flour,  raised  with  baking  powder. 


3o6 


SCIENCE   OF   NUTRITION. 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  1-"ood  Material. 


Vegetable  Foods. 
Cereals,  etc. 
Pie,  pudding,  etc.: 

Pudding,  Indian  meal 
Pudding,  rice  custard. 
Pudding,  tapioca 


Sugars,  starches,  etc. 

Sugar,  granulated 

Sugar,  pulverized 

Sugar,  brown 

Sugar,  maple 

Molasses 

Maple  syrup 

Cornstarch 

Tapioca 

Sago 


Edible  Portion. 


%         % 


60.7 
59-4 
64-5 


Vegetables. 

.Asparagus,  fresh 

.\sparagus,  cooked 

Beans,  Lima,  green 

Beans,  Lima,  dried. . . . 
Beans,  string,  fresh. . . . 
Beans,  string,  cooked*. 
Beans,  white,  dried. . . . 

Beans,  baked 

Beets,  fresh 

Beets,  cooked* 

Beet  "greens,"  cooked* 

Cabbage 

Carrots,  fresh 

Carrots,  evaporated . . . . 

Cauliflower 

Celery 

Sweet  corn,  green 

Cucumbers 

Kgg  plant 

Lettuce 

Onions,  fresh 

Onions,  cooked  •= 

Parsnips 

Peas,  dried 


Available  Nutrients. 


% 


2-5 


55-0 


15.0 
20.0 


20.0 
61.0 
15.0 

15.0 

lO.O 


ii.4 
12.2 


94.0 
91.6 
68.5 
10.4 


1.4 


•7 
i.o 
2.7 
6.7 
1.0 


% 


4-5 
3-2 
2.8 


■3 
7-7 


1-7 

5-3 

12.8 

1-7 
.6 

iS-8 
4.8 
1.2 
1-7 
1-7 
1.2 

•7 
5-8 
1-3 

.8 

2-3 

.6 

•9 

•9 

1.2 

•9 
1.2 

17-3 

*  With  butter,  etc.,  added. 


95-3 

•3    1 

12.6 

7-.S 

68.9 

2.8 

87-.S 

1.0 

88.6 

1.2 

89-5 

1.2 

91-5 

•7 

88.2 

1.0 

3-5 

6.9 

92-3 

•7 

94-5 

.6 

75-4 

1.8 

95-4 

•4 

92.9 

.6 

94-7 

•.=; 

87.6 

.8  ' 

gi.2 

.8 

83.0 

1.2 

9-5 

:   7-b 

% 


4-3 
4.1 
2.9 


% 


26.9 

30-7 
28.2 


1 00.0 
100. o 

95-0 
82.8 
70.0 
71.0 
90.0 
88.0 
78.1 


3-3 
2.1 
21.6 
65.6 
7-2 
1.9 

59-9 

19.6 
9.4 
7.2 
3-2 
5-5 
8.9 

76.9 
4-7 
3-2 

19.0 

3-0 
4.9 
2.9 
9.6 
4.8 
13.0 
62.5 


Uli 


3  ii'=^ii^ 


% 


Calo- 
ries. 


78s 
825 
715 


1790 
1790 
1700 
1485 
1255 
1270 

1715 
1685 
1665 


95 
195 
525 

1565 

180 

90 

1530 
565 
205 
170 
220 
140 
200 

1700 

13s 
80 

445 

75 

120 

85 

215 

175 

290 

1508 


APPENDIX. 


307 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


Kind  of  Food  Material. 


Vegetable  Foods. 
Vegetables. 

Peas,  green 

Peas,  green,  cooked'i^ 

Potatoes 

Potatoes,  cooked,  boiled.. 
Potatoes,      mashed      and 

creamed 

Pumpkins 

Radishes 

Rhubarb 

Squash 

Spinach,  fresh 

Spinach,  cooked* 

Sweet  potatoes,  fresh 

Sweet  potatoes,  cooked*.. 

Tomatoes 

Turnips 

Vegetables  (canned). 

Asparagus 

Beans,  baked 

Beans,  string 

Beans,  Lima 

Sweet  corn 

Peas,  green 

Succotash 

Tomatoes 


Edible  Portion. 


/o 

45 -o 
20.0 


50.0 
30.0 
40.0 
50.0 


Fruits,  etc.  {jresJi). 

Apples '25.0 

Apricots 6.0 

Bananas 35.0 

Blackberries 

Cherries '    5.0 

Cranberries 

Currants !     . . 

Figs I     . . 

Grapes i  25.0 

Huckleberries \     . . 

Lemons i  30.0 

Muskmelons '  50.0 

Oranges !  27.0 


% 

74.6 

73-8 
78.3 

75-5 

i 

7S-I 
93-1 
91.8 
94.4 

,88.3 

(92-3 
89.8 

169.0 
51-9 

I  94-3 
8q.6 


94.4 
68.9 
93-7 
79-5 
76.1 

85-3 
75-9 
94.0 


% 


2.0 
.6 

■7 
.6 

■9 
i.o 

I.I 
2.1 

3-0 
•4 
.8 


.6 

2.7 
•7 
1-7 
1-7 
1.4 
1.8 
•5 


Available  Xuteients. 


7o 


■2  ■  5.2 

•5  '  5.1 

•4  1.7 

•7  I  1.9 


2.0 

•7 
1.0 

■4 
I.I 
1.6 
1.6 

1-3 
2.2 

•7 
1.0 


1.2 

4.8 


2.1 

2.7 

-■7 

•9 


1.6 

•3 

1-5 

•9 

2.7 

1.0 

1-5 

1.0 

2.0 

.8 

1.2 

•3 

1-7 

1.2 

2.2 

1.2 

2.4 

I.I 

2.0 

•S 

1.2 

.8 

I.I 

■S 

1.4 

.6 

1.4 

-5 
.6 


16.7 
14.4 
17.7 
20.0 

17. 1 

5-0 
5-6 

3-5 
8.6 

3-2 
2.7 
26.2 
40.3 
3-8 
7.8 


2.8 
19.7 

3-7 
14-3 
18.3 

9.6 
18.0 

3-9 


12. » 

12.2 

19.9 

9.9 

I5-I 
8.9 

II. 6 
17.0 

17-3 
14.9 

7-7 

8.4 

10.5 


% 

.8 

I.I 

.8 

.8 


■5 
.8 

•S 
.6 
1.6 
I.I 
.8 
•7 
•4 
.6 


Calo- 
ries. 

430 
490 

370 
415 

475 
no 
130 
100 
205 
100 
235 
545 
885 
100 
175 


80 

555 
90 

335 
430 
235 
425 
100 


260 
240 
400 

235 
320 
190 
230 
330 
390 
300 
180 
160 
210 


*  With  butter,  etc.,  added. 


3o8 


SCIENCE   OF   NUTRITION. 


COMPOSITION  OF  ORDINARY  FOOD  MATERIALS  (Continued). 


KiNn  OF  Food  Material. 


Edible  Portion. 


Available  Nvtrients. 


a  « 


Vegetable  Foods.          %  %  % 
Fruits,  etc.  (fresh). 

Pears.. lo.o  84.4 

Plums 50  I  78-4 

Prunes 6.0  79.6  2.1 

Raspberries,  black .-  84.1  1.7 

Strawberries 5.0  1  90.4  i.o 

Watermelons 60.0  [92.4  .9 

Fruits,  etc.  (dried).        I 

Apples ..  28.1  7.5 

Apricots I     --  29.4  7.7 

Citron 1     --  i9-o  8.3 

Currants '     ..  17-2  8.6 

Dates lo.o  15.4  8.8 

Figs J18.8  8.7 

Raisins lo.o  14.6  9.1 

Prunes 15.0  22.3  8.3 

Fruits,  etc.  (canned). 

Apricots '     ..  Si. 4  1.9 

Blackberries 40.0  '    6.1 

Blueberries ..  85.6  j    1.6 

Cherries 77-2  2.3 

Crab-apples 42.4  5.7 

Peaches 88.1  1.3 

Pears ;     ..  81. i  i.g 

Strawberries  (stewed) ..  74.8  2.6 

Nuts. 

Almonds 45.0  4.8  10.9 

Butternuts 86.0  4.4  11.4 

Chestnuts  (fresh) 16.0  45.0  5.9 

Cocoanuts 49.0  14.1  9.2 

p-ilberts 52.0  '    3.7  10.7 

Hickor}-nuts 62.0  3.7  10.6 

Peanuts 25.0  9.2   j  10.7 


%        % 


■7 
1.4 


1-3 
3-7 
•4 
1.9 
1.6 

3-4 
2.0 
1.6 


17.8 
23-7 
5-3  ■ 
4.8 

13-1 
21.9 


2.0 

•9 

1-3 

1-5 

2-5 

•3 
3-0 


49.4 

55-1 
4.9 

45-5 
58.8 
60.7 
34-7 


7b 

12.7 
18.2 
17. 1 
11.4 
6.8 
6.0 


59-6 
56.5 
70-3 
67.0 
70.7 
67.0 
68.7 
66.1 


15-7 
50-9 

19. 1 
49.0 
9.8 
16.2 
21.7 


15.6 
3-2 
37-9 
25-1 
11.7 
10.3 
22.0 


% 


1-5 
1.8 

•7 
3-8 
1.0 
1.8 
2.6 
1-7 


i-S 
2.2 
1.0 

1-3 
1.8 
1.6 
1-5 


Calo- 
ries. 

255 
345 
325 
270 
160 
125 


1 190 
1 130 

1340 
1315 
1415 
1290 
1410 
1230 


295 
1015 
240 
365 
98s 
190 
310 
400 


2685 
2805 
990 
2460 
2930 
2980 
2255 


For  greater  detail  see  The  Chemical  Composition  of 
American  Food  ]Materials,  by  Atwater  and  Bryant,  Bulletin  28 
(Revised),  U.  S.  Dept.  of  Agriculture,  Washington,  1902. 


INDEX  OF  AUTHORS. 


Abdeehalden    on     composition     of 
proteid,  289 
on  diet,  183 

on  effect  of  altitude  on  erythrocytes, 
222 
Abderhalden  and  Bergell,  290 
Abderhalden  and  Rona,  104,  105 
Abderhalden  and  Teruuchi,  292 
Almagia  on  gout,  285 

on  purin  metabolism,  275,  276 
Anderson,  224 
Anderson  and  Bergman,  223 
Araki,  214,  248 
Armsby,  42 

Armstrong  and  Folin,  115 
Arteaga,  229 
Ascoli,  274 

Atwater  on  calorimeter,  42 
on  diet,  178,  187 

on  modification  of  Rubner's  stand- 
ard values,  40 
Atwater  and  Benedict,  168,  190 
Atwater  and  Bryant  on  composition 
of  food  materials,  300,  308 
on     modification     of     Rubner's 
standard  values,  40 


Babak,  87 

Bachl,  21 

Bauer,  213 

Beebe,  283 

Beger,  Morgen,  and  Fingerling,  199 

Bendix  and  Schittenhelm,  276  , 

Benedict  on  alcohol,  192 

on  cutaneous  excretions,  21 

on  foodstuffs,  141 
Benedict  and  Atwater,  168 
Benjamin,  268 

Bergell  and  Abderhalden,  290 
Berger,  112 

Bergman  and  Anderson,  223 
Bernard  on  dextrose,  248 

on  glycogen  from  proteid,  109,  120 
Bernard's  diabetic  center,  225,  226 

piqure,  225,  226 
Berthelot,  141 
Billstrom,  Johansson,  and  Heyl,  153 


Bischoff  and  Voit  on  gelatin,  102 
on  heat  value  of  metabolism,  34 
on  influence  of  proteid  food,  99 
on  nitrogen  in  urine,  23 
on  production  of  feces,  46,  47 

Blauberg,  203 

Bleibtreu,  152 

Blum,  115 

Bornstein,  loi,  166 

Bowen  and  Highby,  170 

Breithaupt,  49 

Breuer  and  Seiller,  222 

Broden  and  Wolpert,  163 

Brugsch,  63 

Brunton,  274 

Bryant  and  Atwater  on  composition 
of  food  materials,  300,  308 
on     modification     of     Rubner's 
standard  values,  40 

Bunge  on  the  ash  of  milk,  202 

on  relationship  between  rapidity  of 
growth  and  longevity,  211 

Burckhardt,  70 

Biirgi,  119,  175 

Burian  on  purin  metabolism,  280,  281, 
282,  294 

Burian  and  Schur,  268,  276,  277,  278, 
279,  281 


Camerer,  202 
Camerer  (W.  Jr.),  207 
Caspari,  173,  222 
Castero  and  Schultze,  290 
Cetti,  49,  58 
Chapin,  204 

Chittenden  on  diet,  167,  179,  180,  181, 
182,  185,  186,  187 

on  nitrogen  equilibrium,   157 

on  purin  metabolism,  278 
Clapp,   180 
Cohnheim,   105 
Crawford,  32 
Cremer  on  collection  of  feces,  46 

on  the  formation  of  milk  sugar,  200 

on  influence  of  proteid  food,   121, 
122,  123 

on  metabolism  in  diabetes,  233,  245 


309 


3IO 


INDEX   OF    AUTHORS. 


Cushney,   192 


Daval  and  Patein,  204 
Dean  and  Henderson,   103 
Deprctz,  32,  53 
Dobson,  225 
DuBois-Reymond,   176 
Dulong,  32,  37, 

Durig  and  Zuntz   on    metabolism    at 
high  altitudes,  216,  219,  220,  221 


Edkins  and  Langley,  69 
Ellinger,   117 
Embden,  232,  292 

Embden  and  Salomon  on  metabolism 
in  diabetes,  229,  231,  232 


Falta,  116 

Falta  and  Neubauer,  116 

Farkas,  193 

Feder,  106 

Fick  and  Wislicenus,  165 

Fingerling,   197 

Fingerling,  Beger,  and  Morgen,   199 

Finkler,  213 

Fischer  (B.)    on   metabolism    in  dia- 
betes, 246 

Fischer  (E.)  on  peptids,  293 
on  purin  metabolism,   270 

Flourens's  law  of  longevity,  211 

Folin  on  diet,  183 

on  influence  of  proteid  food,  118 
of   sugar  on   metabolism,    150 
on  metabolism,  291,  292,  293 

Folin  and  Armstrong,   115 

Fraenkel  and  Geppert,  216 

Frank  and  Trommsdorf,  107 

Frank  and  Voit,  82 

Frentzcl,  72 

Frentzel  and  Reach,  171 

Freund  (E.),  61,  62 

Freund  (O.),  61,  62 

Friedenthal,  296 

Friedjung  and  Jolles,  203 

Friedmann,  115 


Garrod,  282 
Garrod  and  Hale,  116 
Geelmuyden,  238,  294 
Geppert  and  Fraenkel,  216 
Geppert  and  Speck,  215 
Gies  and  Hawk,  213 
Gogitidse,  200 
Goldbraith  and  Simpson,  77 


Graham,  180 

system  of  vegetarianism,  180 
Gruber,  106,  117 
Grund,  244 


Hageman  and  Zuntz,  32 

Hahn,  276 

Hale  and  Garrod,  116 

Halsey,  no.  231 

Hammarsten,  244 

Hanriot   and   Richct,   58 

Hansen   and   Henriques,    104 

Harrold  and   Lee,    169 

Hartogh  and  Schumm,  232 

Hasselbalch,  194 

Hawk,  106 

Hawk   and   Gies,    213 

Hawk  and  Sherman,  119 

Heilner,  106 

Heineman,   167 

Hellesen,    169,    170 

Helmholtz,  33 

Henderson  and  Dean,   103 

Henriques  and  Hansen,    104 

Herring  and  Simpson,  79 

Herter  and  Wakeman,  238 

Herter  and  Wilbur,   239 

Heubner,  207,  208 

Heubner  and  Rubner,  203,  204,  205, 

207 
Heyl,  Johansson,  and  Billstrom,  153 
Highby  and  Bowen,  170 
Hirsch,   Miiller,   and  Roily,   252 
Hirschfeld,   182 
Hofmeister,  226,  289 
Horbaczewski,  272,  273 
Hosslin,    261 


Inagaki   and  Schwenkenbecker,  257 


Jacksch  on  metabolism  in   diabetes, 

245 
in  phosphorus-poisoning,  247 

in  fever,  268 
Jackson,  229 

Jackson  and  Mandel,   244 
Jackson  and  Mendel,  117 
Jacoby,  247 
Jaffe,  183 

Janeway  an4  Oertcl,  246 
Jensen,  149 

Johansson   on   regulation   of  temper- 
ature, 92 
on  starvation,   58,  74,  76 
Johansson  and  Koraen,  170 


INDEX   OF   AUTHORS. 


311 


Johansson,  Billstrom,  and  Heyl,   153 

Jolles  and   Friedjung,   203 

Jones,   273 

Jones  and  Partridge,  273 

Jones  and  Winternitz,  292 

Joslin,  239 


Katzenstein,  171,  173 

Kauffmann,  103 

Kermauer,   49,  50 

Kiesel,  202 

Kirchmann,  102 

Klemperer  267,  284 

Klemperer  and  von  Leyden  on  metab- 
olism in  fever,  261,  262,  263,  265 

Knopf,  no,  231 

Kohler,  215 

Koraen   and  Johansson,    170 

Korkunoff  and  E.  Voit,  99,  144 

Kossel  on  metabolism,  289 
on  starvation,  56 

on  sugar  from  proteid  in  diabetes, 
no 

Kossel  and  Steudel,  272 

Krehl,  256,  257,  258 

Krehl  and  Mathes,   267 

Kriiger  and  Schmid,  273 

Krummacher  on  influence  of  mechan- 
ical work  on  metabolism,  165, 
166 
of  proteid  food,  102 

Kiilz  on  influence  of  proteid  food,  102 
on   ingestion   of  fat   and   carbohy- 
drate, 149 
on  starvation,  71 

Kumagawa,  53 


Landergeen  on  ingestion  of  fat  and 
carbohydrate,  150,  156,  157 

on  starvation,  59 
Landois,  55 
Lang,  257 

Langley  and  Edkins,  69 
Langstein  and  Meyer,  116 
Langstein  and  Neuberg,  292 
Langworthy,   299 
La  Place,  18 
La  Place   and  Lavoisier   on   animal 

heat,  31 
Lavoisier,  18,  19,  20,  31,  32 
Lavoisier  and  La  Place,  31 
Lavonius,  174,  185 
Lee  and  Harrold,  169 
Lefevre,  92,  254 
Lehmann  and  E.  Voit,  151 


Lehmann  and  Zuntz,  58 

Lemaire,  201 

Lesser,  103 

Levene,  289 

Levene  and  Mandel,  271 

Lewenstein,  215 

Lewinski,   70 

Leyden    and    Klemperer  on  metabo- 
lism in  fever,  261,  262,  263,  265 

Lichtenfelt,   178,  182 

Liebermeister,  257 

Liebig  on  atmospheric  pressure,  212 
on  chemistry  of  carbon  compounds, 

19,  20 
on  nutrition,    18 
on  oxygen,   19 

Lindemann  and  May,  245 

Linser  and  Schmid,  250,  251 

Litten,   266 

Loewi  on  colloid  sugar,  227 
on  ingestion  of  amino  acids,  103 
on  purin   metabolism,   280 

Loewy,  on  effect  of   altitude  on  hem- 
oglobin, 222 
on    increased    excretion    of    amino 
■  acids  at  high  altitudes,  221 

Loewy  and  Zuntz,  217,  220 

Lorisch,  51 

Luciani  on  starvation,  61,  69,  74 

Ludwig,  19 

Lusk  on  alcohol,  192 

on  carbohydrate  ingestion,  154 
on  fat  content  of  milk,  201 
on  influence  of  diabetes  on  proteid 
metabolism,  235 
of  food  on  composition  of  milk, 

199 
of  work  on  metabolism,  169 
on  metabolism  in  diabetes,  229,  236 
on  starvation,  70,  71 
Lusk  and  Mandel  on  levulose  in  dia- 
betes, 243 
on  metabolism  in  diabetes,  230, 
232,  233,  241 
Lusk  and  Parker,  64,  114 
Lusk    and    Stiles    on    metabolism    in 
diabetes,  227,  230,  231 
on  proteid  food,  104,  no 
on  starvation,  64 
Lusk,  Ray,  and  McDermott,  247 
Lusk,  Reilly,  and  Nolan  on  influence 
of  proteid  food,  102,  in 
on     metabolism     in     diabetes, 
229,  230,  235 
Liithje   on   influence   of  ingestion   of 
fat  and  carbohydrate,  159 
on  metabolism  in  diabetes,  230 
in  myxedema,  222 


;i2 


INDEX    OF   AUTHORS. 


Luzzatto,  245 


Magnus,  19 

Magnus-Levy    on    food    requirement 
during  growth,  194,  195 
on  gout,  283 

on  influence  of  proteid  food,  114 
on    metabolism    in    diabetes,    238, 

239 

in  myxedema,   223 
Mallet,  118 

Mandel   (A.  R.)    on     metabolism    in 
diabetes,  247,  292 

in  fever,  267,  268,  269 
on  starvation,  56 
Mandel  (A.  R.)  and  Lusk  on  levulose 
in  diabetes,  243 

on  metabolism  in  diabetes,  230, 
232,  233,  241 
Mandel   (J.  A.)  and  Jackson,   244 
Mandel  (J.  A.)  and  Levene,  271 
Mansfield  and  Woods  on  diet,  178,  187 

on  influence  of  mechanical  work 
on  nutrition,  169 
Mariott  and  Wolf,  115 
Massen,  276 
Mathes  and  Krehl,  267 
May  on  metabolism  in  fever,  253,  258, 

260 
May  and  Lindcmann,  245 
Mayer,    33,  231 

McDermott,  Rav,  and  Lusk,  247 
Meeh,  80 

Meissl  and  Strohmer,  150 
Meltzer,  192 
Mendel,  179,  271 
Mendel  and  Jackson,  117 
Mendel  and  White,  276 
Mendelson,  256 
Mering,  227 

Mering  and  Minkowski,  225 
Mering  and  Zuntz,  124 
Merlotti,  53 

Meyer  and  Langstein,   116 
Miescher   on    starvation,  55,   56.  67, 

143 

Minkowski  on  gout,  283,  287 
on  increase  of  uric  acid,  272 
on  levulose  in  diabetes,  243 
on  metabolism  in  diabetes,  225,  228, 

229,  240 
on   purin   metabolism,   280 

Minkowski  and  von  Mering,  225 

Moeller,  49 

Mohr,  267 

Morgen,  Beger,  and  Fingerling,  199 

Moritz,  226,  227 


Muller  (Franz)  on  effect   of   altitude 
on  hemoglobin,  222 
of    mechanical  work    on  metab- 
olism, 173 
Muller  (Friedrich)  on  effect  of  proteid 
food,  no 
on  feces,  49 
on    metabolism    in  carcinoma, 

in  fever,  260 
in  myxedema,   223 
MiJller,  Hirsch,  and  Roily,  252 
Munk  on  diet,    179 

on  influence  of  proteid  food,  118 
on  starvation,  61,  62 
Murlin,  158 


Naunyx,  266 
Nebelthau,  255,  256 
Nencki,  276 

Nencki  and  Schultzen,  291 
Nencki  and  Zaleski,  291 
Neubauer,    243 
Neubauer  and  Falta,  116 
Neuberg,  244,  245 
Neuberg  and  Langstein,  292 
Neuberg  and  Salkowski,  244 
Nolan,  Reilly,  and  Lusk  on  influence 
of  proteid  food,   102,    in 
on     metabolism     in     diabetes, 
229,  230,  235 


Oertel  and  Janeway,  246 
Opie,  245 
Oppenhcimer,  208 
Osborne,  289 
Oswald,  247 

Parker  and  Lusk,  64,  114 

Partridge  and  Jones,  273 

Patein  and  Daval,  204 

Pawlow,  276 

Pembrey,   152 

Pettenkofer,  respiration  apparatus  of, 

22,  23 
Pettenkofer  and  Voit   on   heat  value 
of  metabolism,  34,  35 
on    influence    of    work    on    me- 
tabolism. 160 
on  metabolism  in  leukocythemia, 
214 
in  starvation,  24,  25,  26,  27 
on  proteid  food,  120 
on  respiration  in  diabetes,  235 
on  respiratory  quotient,  27,  28 
on  starvation,  73 


INDEX  OF  AUTHORS. 


313 


Pfeiffer,  274 
Pfeil,  282 
Pfluger,  30 

on   effect   of  temperature    on    me- 
tabolism,  250 
on  metabolism  in  diabetes,  228,  230, 

231 
on  proteid  food,  98,  121 
on  respiration  and  metabolism,  30 
on  theory  of  metabolism,  288 
Prausnitz  on  digestibility  of  carbohy- 
drates, 49,  50,  51 
on  feces,  49 
on  starvation,  53,  71 


Ranke,    183 

Ray,   McDermott,   and  Lusk,   247 
Reach    and  Jrentzel,    171 
Regnault  and  Reiset  on  respiration, 

20,  22 
Reilly,  Nolan,  and  Lusk  on  influence 
of  proteid  food,  102,  in 
on     metabolism     in     diabetes, 
229,  230,  235 
Reiset  and  Regnault  on  respiration, 

20,  22 
Rheinboldt,  223 
Richet  and  Hanriot,   58 
Rieder,  49 
Riethus,  258,  259 
Rietschel,    118 
Rock  wood,  277,  282 
Rohrig  and  Zuntz,  82 
Roily,   252 

Roily,   Hirsch,   and  Miiller,   252 
Rona    and    Abderhalden    on    proteid 

food,  104,  105 
Rosenfeld,  143,  246 
Rosenheim,  179 
Rost,  210 

Rubner  on  animal  calorimeter,  41 
on  caloric  value  of  feces,  36,  37 
of   proteid   in   nutrition,    38 
of  urine,  36 
on   carbon   retention   after   proteid 

ingestion,  122,  123 
on  collection  of  feces,  46 
on    comparison   of   estimated   heat 
from  metabolism  with  heat  actu- 
ally produced,  41 
on  compensation  theory,   125 
on  diet,  178,  184,  187,  188,  189,  190 
on   digestibility   of   vegetables   and 

cereals,   49 
on  fuel  value  of  feces,  51 
on  heat  value  of  carbohydrates,  40 
of  metabolism,  35,  36,  38,  39 


Rubner  on  influence  of  temperature  on 

proteid  metabolism,  128,    129, 

130. 

of  work  on  metabolism,  162,  163 

on  ingestion  of  carbohydrates,  T49, 

153.   158 
of  fat,   143,  144,  145,  146 
on  metabolism  after  proteid  inges- 
tion  in   excess,    124,   125 
in  diabetes,   237 
of  children,   205 
on  percentage  composition  of  cow's 

and  human  milk,   203,   204 
on  physiological  utilization  of  total 

calories   of   milk,    203 
on  proteid  food,  loi,   119,   121 
on  specific  dynamic  action  of  food- 
stuffs, 133,  134,  135,  136, 
i37>  138,  139.  140 
of   proteid,    126 
on    stages   of   proteid    metabolism, 

127 
on  temperature,  81,  82,  83,  84,  85, 
86,  87,  88,  89,  90,  92,  93,  94,  95, 

96,  97 
on  theory  of  metabolism,  294,  295 
on    variation    in    metabolism    after 

meat    ingestion,    108 
on  water  hunger,  52 
Rubner  and  Heubner  on  food  require- 
ment during  growth,  203,  204,  205, 
207 


Salkowski,  270,  275 

Salkowski  and  Neuberg,  244 

Salomon,  271 

Salomon  and  Embden  on  metabolism 

and  diabetes,   229 
Sanctorius,    1 7 
Sanford  and  Wilson,  208 
Sawadowsky,   256 
Schafer,   200 
Scheele,    270 
Schittenhelm,  274 
Schittenhelm  and   Bendix,   276 
Schleich,  251 

Schliep  and  von  Noorden,  286 
Schlossmann,  205 
Schmid  and  Kriiger,  273 
Schmid  and  Linser,   250,   251 
Schondorff,  66,  148 
Schryver,  248 
Schultz,  68 

Schultze  and  Castero,  290 
Schultzen  and  Nencki,  291 
Schulz,  143 
Schumburg,  169,   170 


114 


INDEX  OF  AUTHORS. 


Schumburg  and  Zuntz,  174,  219 
Schumm   and    Hartogh,    232 
Schur    and    Burian    on    metabolism 
in  fever,  268 
on  purin  metabolism,  276,   277, 
278,  279,  281 
Schiirmann,  35 
Schwarz,  239 

Schwcnkenbecker   and    Inagaki,    257 
Seelig,  234 

Seiller  and   Breuer,   222 
Sherman   and   Hawk,    119 
Simpson  and  Goldbraith,  77 
Simpson   and   Herring,   79 
Siven,  154,  178 
Slemons,  196,  197 
Slowtzoff,  172 
Soetbeer,  285 
Sonden,  59 

Sonden  and  Tigerstedt,  74,  76 
Speck  and  Geppert,  215 
Spitzer,  272 
Steudel,   280 
Steudel  and  Kossel,  272 
StUes   and   Lusk   on   metabolism   in 
diabetes,  227,  230,  231 
on  proteid  food,  104,  no 
on  starvation,  64 
Stockvis,  274 
Stohmann,  35 

Stohmann  on  heat  value  of  carbohy- 
drates, 40 
Stoklasa,  294 

Straub  on  influence  of  proteid  food, 
106 
on  metabolism  in  diabetes,   235 
on  water  hunger,  52 
Strohmer  and  Meissl,   150 
Susruta,   225 
Sydenham,  282 


Tallquist,  155 

Tangl,  193 

Tanner,  53 

Temesvary.  201 

Terray,  216 

Teruuchi  and   Abderhalden,   292 

Tigerstedt,   59,   73 

Tigerstedt  and  Sonden,  74,  76 

Traube,    254 

Trommsdorf  and  Frank,  107 

Tuczec,  61 


VlAULT,    221 

Virchow,  246 

Voit  (C.)  on  collection  of  feces,  45,  46 


Voit  (C.)  on  creatin,  117 
on  diet,   177,   182,  185 
on  gelatin,   57 
on  hair  and  epidermis,  21 
on  heat  value  of  metabolism,  34,  35 
on  influence  of  food  on  composition 

of  milk,  198 
of  ingesting  increasing  quantities 

of  meat,  10 1 
on  ingestion  of  carbohydrate,   148, 

149-   150 

of  fat,  142,  145 
on  metabolism,  28,  29,  42 
on  nitrogen  equilibrium,  20 

gas,  21 

in  milk  and  urine,   197 
on  organs  attacked  in  starvation,  69 
on  proteid  food,  105,  106,  109 
on  rise  in  carbon  dioxid  excretion, 

124 
on  secondary  rise  in  proteid  metab- 
olism, 145 
on  temperature,  91,  92 
on  theory  of  metabolism,  288 
on  total  carbon  excretion,   22 
on  urea  elimination  in  starvation, 

54,  55 
Voit  (,C.)  and  Bischoff  on  gelatm,  102 
on  heat  value  of  metabolism,  34 
on  influence  of  proteid  food,  99 
on  nitrogen  in  urine,  23 
on  production  of  feces,  46,  47 
Voit    (C.)   and  Pettenkofer    on    heat 
value  of  metabolism,  34,  35 
on  influence  of  work  on  metab- 
olism, 160 
on  metabolism  in  leukocythemia, 
214 
Voit  (C.)  and  Pettenkofer  on  metabo- 
lism in  starvation,  24,  25,  26,  27 
on  proteid  food,  120 
on  respiration  in  diabetes,  235 
on  respiratory  quotient,  27,  28 
on  starvation,  73 
Voit   (E.)   on  cause    of    death    from 
starvation,  67,  68 
on  energy  requirements  in  starva- 
tion, 60 
on  frog's  carbon  dioxid  elimination 

at  various  temperatures,  78,  79 
on    heat    production    at    medium 

temperatures,  81 
on  ingestion  of  carbohydrates,  152, 

154 
on  metabolism  in  diabetes,  236 
on  nitrogen  metabolism,  57 
on  starvation,  65,   66,   69 
on  temperature,  87 


INDEX   OF  AUTHORS. 


;i5 


Voit  (E.)  and  Korkunoff,  99,  I44 
Voit  (E.)  and  Lehmann,  151 
Voit  (F.)  on  metabolism  in  fever,  251 
in  myxedema,   223 
on  source  of  feces,  47,  48 
Voit  (F.)  and  Frank,  82 
Von  Hosslin  on  metabolism  in  fever, 

261 
Von  Leyden  and  Klemperer  on  metab- 
olism in  fever,  261,  262,  263,  265 
Von  Mering,  227 
Von  Mering  and  Minkowski,  225 
Von  Noorden  on  metabolism  in  dia- 
betes, 231,  233,  239,  240,  243 
on  opium  in  diabetes,  242 
Von  Noorden  and  Schliep,  286 
Von  Schrotter  and  Zuntz,  217 
Von  Terray,  216 
Von  Winckel,    195 


Wakeman,  290 

Wakeman  and  Herter,  238 

Waldvogel,  247 

Weinland,  152 

Welch,  266 

White,  204 

White  and  Mendel,  276 

Wiener,  274,  280 

Wilbur  and  Herter,  239 

Willis,  225 

Wilson,  209,  210 

Wilson  and  Sanford,  208 

Winckel,   195 

Winternitz  and  Jones,  292 

Wislicenus   and  Fick,    165 

Wolf,  115,  292 

Wolf  andMariott,  115 

Wolffberg,    109 

Wolgemuth,  290 

Wollaston,   270 


Wolpert,  93 

Wolpert  and  Broden,  163 
Wood,  254 

Woods  and  Mansfield  on  diet,    178, 
187 
on  influence  of  mechanical  work 
on  metabolism,  169 
Workman,   219 


Zacharjewski,  195,  196 
Zaleski  and  Nencki,  291 
Ziegler,  266 
Zitowitsch,   191 

Zuntz   on  effect  of  altitude  on  hem- 
oglobin, 222 
of   mechanical  work   on   metab- 
olism,  167,   173 
of     mountaineering     on    metab- 
olism, 218 
of  training  on  metabolism,  175 
on  metabolism  in  anemia,  212 
on    renal    character    of    phlorhizin 

glycosuria,   227 
on  starvation,   71 
on  temperature,  97 
Zuntz  (L.),  217,  218 
Zuntz    and    Durig  on  effect  of  alti- 
tude on  metabolism,  216, 
221 
on  respiration,  219 
on     saturation     of     hemoglobin 
within  blood  at  different  alti- 
tudes,   220' 
Zuntz  and  Hageman,  32 
Zuntz  and  Lehmann,  58 
Zuntz  and  Loewy,  217 
Zuntz  and  von  Mering,  124 
Zuntz  and  Rohrig,  82 
Zuntz  and  Schumburg,  174,  219 
Zuntz  and  Von  Schrotter,  217 


INDEX  OF  SUBJECTS. 


Abundant,  diet,  125 
Acetoacetic  acid  in  diabetes,  238 
Acetolase,  294 

Acetone  in  diabetes,  238,  239 
Acetonuria  in  starvation,   63 
Acid,  acetoacetic,  in  diabetes,  238 
/?-oxy butyric,  in  diabetes,  238,  239 

in  urine,  in  starvation,  63 
(f-glucuronic,  244 
hippuric,  in  urine,  64,  114 
kynurenic,  in  urine,   117 
lactic,     conversion     of,     into     dex- 
trose, 232 
in  urine  after  bloodletting,  214 
phosphoric,    in    urine,    in    starva- 
tion, 62 
uric,  270,  271 

conversion  of  adenin  into,  274 
of  guanin  into,  274 
of  hypoxanthin  into,  272 
into  urea,   275 
elimination   of,   effect   of  adenin 

on,  272 
endogenous,  277 

excretion    of,    endogenous,    con- 
stancy of,  278 
exogenous,   277 

power     of     crushed     tissue     to 
destroy,  274 
a-colloid  dextrose,  234 
Adenin,  270,  271 

conversion  of,  into  uric  acid,  274 
effect  on  uric  acid  elimination,  272 
a-dextrose,  234 
Alanin,  141,  231 
Alanyl-alanin,  293 
Alanyl-glycin,  293 
Albuminuria  in  starvation,  63 
Alcaptonuria,  phenylalanin  in,  116 
ratio    between    homogentisic     acid 
and  nitrogen  elimination  in  urine 
in,  116 
tyrosin  in,   116 
Alcohol,  effect  on  metabohsm,  190,  191 
on  oxidative  power  of  liver  for 

uric  acid,  30 
on  purin  metabolism,  283 
food  value  of,  191 


Alcohol,  stimulating  action  of,  170 
Alcoholase,  294 
Alimentary  glycosuria,  226,  228 
Allantoin  in  urine,  272,  275,  276 
Altitude,  high,  effect  on  metabolism, 
216,  217,  218 
on  red  blood-cells,  221 
increase    of    hemoglobin    at,  222 
Amino   bodies,   regeneration   of,   into 

proteid,  291 
Ammonia,  21 

nitrogen  in  urine  in  starvation,  63 
Anabolism,  19 
Anemia,  metabolism  in,  212 
Apnea,  30 

Arabinose  in  diabetes,   245 
Aseptic  fever,  249 
Ash   of  milk,   percentage   absorption 

of,  203 
Asparagin,     effect     of,     on     dextrose 

output  in  diabetes,  231 
Atmosphere,  pressure  of,  216 

relative  composition  of,  216 


Basic   requirement    of    an  organism, 
90.  91 

Baths,  cold,  influence  of,  on  metabol- 
ism, 92,  93 

6-colloid  dextrose,  234 

6-dextrose,  234 

Bile  in  starvation,  69 

Blood,  dextrose  in,  in  starvation,  70 
globulin  in,  in  starvation,  70 
hyperarterialization  of,  30 
in  starvation,  70 

Blood-cells,   red,   effect  of  high   alti- 
tude on,  221 

Blood-corpuscles  in  starvation,  70 

Bloodletting,     lactic     acid     in     urine 
after,  214 

Blood-plasma  in  starvation,   70 

Bone  feces,  45 

/?-oxybutYric  acid  in  diabetes,  238,  239 
in  urine  in  starvation,  63 

Boyhood,  metabolism  in,  146 

Bread,  influence  on  meat  feces,  47 
particles  in  feces,  49 


317 


3i8 


INDEX  OF  SUBJECTS. 


Caffein,  273 

Calories,  in    milk,    percentage    distri- 
bution of,  204 
percentage    of,    in    different    diets, 
138 

Calorific  value  of  milk,  205 

of  proteid  in  nutrition,  36,  38 

Cane  sugar,  influence  on  metabolism, 

150 
Carbohydrate,  effect  in  typhoid  fever, 
264 

metabolism,    influence   of   J-glucu- 
ronic   acid  and  pentoses  on,  244 
Carbohydrates   and    fat    interdiange- 
able  in  nutrition,  35 

as  fuel  for  production  of  mechani- 
cal energy  by  body,  167 

conversion  of,  into    fat,    150,    151, 

digestibility  of,   49 
heat  value  of,  40 
ingestion  of,  influence,   142,  147 
nitrogen   equilibrium   after,    154, 

sudden  withdrawal  of,  susceptibil- 
ity of  proteid  metabolism  to,  154 
Carbon  dioxid  elimination,    day  and 
night,  in  starvation,  74 
from  mechanical  work,    170 
in  respiration,  30 
in  starvation,    58 
volume  expired,  relation  to  vol- 
ume of  oxygen  inspired,  27 
equilibrium,  loi 
monoxid  diabetes,  234 
ratio  of  nitrogen  to,  in  urine,  36 
retention    after    proteid    ingestion, 
122,  123 
Carcinoma,  metabolism  in,  258,  260 
Casein,   39 

Castration,  effect  on  metabolism,  222 
Catabolism,  19 
Cells  in   metabolism,  42 
Chemical  regulation  of  temperature, 
80,83 
in  dog,  85 
in  guinea-pig,  84 
Children,  metabolism  of,  205,  206 
Chlorin  in  urine  in  starvation,  63 
Circulating  proteid,  55 

in  star%'ation,  55,  56 
Climate,  influence  on  metabolism,  97 
Clonic    convulsions    after    thyroidec- 
tomy, 224 
Clothes,  effect  of,  on  heat  regulation, 
96 
on  metabolism,  96 
Coffee,  stimulating  action   of,    170 


Cold  baths,  influence  of,  on  metabol- 
ism, 92,  93 
Cold,  effect  of,  on  metabolism,  83 

in  fever,  258 
Colloid  sugar,   227 
Compensation  theory,  125,  133 
Composition  of  food  materials,   300 

308 
Convulsions,   clonic,   after  ihyroidec 

tomy,  224 
Corpora  striata,  heat  puncture  of,  252 
Cost  of  proteid  and  energy,  299 
Creatin  in  urine,  117,  118 
Creatinin     elimination     after     meat 
ingestion,  118 

in  urine,  117 
Creatinin-nitrogen  in  urine,  118 
Critical  temperature,  84 
Croupous  pneumonia,  epicritical  nitro- 
gen elimination  in,  260 
metabolism  in,  260 
Crushed  tissue,  power  of,  to  destroy 

uric  acid,  274 
Curare,    eft'ect    of,    on    regulation    of 

temperature,  82 
Cutaneous  excretions,  amount  of,  21 
Cystein,  115 
Cystinuria,   115 


Dampness,  effect  on  metabolism,  88 
Death,  cause  of,  in  starvation,  67 
Degeneration,  fatty,  in  fevers,  266 
of  proteid,  246,  247 
parenchymatous,  in  fevers,  266 
Deposit  proteid,  159 
Dextrose,    conversion    of    lactic    acid 
into,  232 
elimination    and    urinary    nitrogen 
in     diabetes,     relation     between, 
228,  229 
excretion  of,  before  and  after  meat 

ingestion  in  diabetes,  in 
in  blood  in  starvation,  70 
in  diabetes,  effect  of  asparagin  on 
output  of,  231 
fat  metabolism,  as  source  of,  230, 

231.233 
in  urine  in  starvation,  63 
production    and    nitrogen    elimina- 
tion   in     starvation,    constant 
ratio  between,  64 
from  proteid  in  diabetes,   238 
d-glucuronic  acid,  influence  of,  on 
carbohydrate  metabolism,  244 
Diabetes,   acetoacetic  acid   in,   238 
acetone  in,  238,  239 


INDEX  OF  SUBJECTS. 


319 


Diabetes,  arabinose  in,  245 
/?-oxybutyric  acid  in,  238,  239 
carbon  monoxid,  234 
causes  of,  226 
dextrose    in,     fat     metabolism     as 

source  of,  230,  231,  233 
emaciation  in,  234 
energy  value  of  proteid  in,  237 
excretion  of  dextrose  and  nitrogen 

before  and  after  meat   ingestion 

in.  III 
experimental  pancreas,   226 
fatal  ratio  in,  241 
fatty    degeneration    of    proteid    in, 

246, 247 
glycogen  in,  240 

influence   of  asparagin  on  dextrose 
output  in,  231 

on  proteid  metabolism,  235 
levulose  in,  243 
mellitus,  226 
metabolism  in,  225 
methods  for  examising  severe  types, 

240,  241 
opium  in,  242 

production   of   dextrose   from   pro- 
teid in,  238 
relation   between   urinary   nitrogen 

and  sugar   elimination    in,    228, 

229 
rhamnose  in,  245 
starvation,  226 
sugar  from  proteid  in,  no 
yeast  in,  243 
Diabetic  center,  225,  226 
Dialanyl-cystin,  293 
Diet,  abundant,  125 

high    in    carbohydrate    in    typhoid 
fever,  264 

in  proteid  in  typhoid  fever,  263 
in  fevers,   261 
in  gout,  287 
in  pregnancy,    195 
influence    of,    on    composition    of 

milk,  198,  200 
maintenance,   125 

meat-fat    absence  of  secondary  rise 
in  fat  metabolism  on,  14^ 

secondary  rise  in  proteid  metab- 
olism on,  145 
milk,  in  fevers,  261 

results  of,   190 
normal,  177 
purin-free,  277 
Dietaries,  hospital,   188 

standard,   187,   188 
Diets,  percentage  of  calories  in,  138 
Digestibility   of   carbohydrates,    49 


Drinking  water  copiously,  action  of, 
106 
effect  on  proteid  metabolism,  105 
Dynamic  action  of  metabolism,  41 
secondary,    absence    of,    in    fat 
metabolism  on  meat-fat  diet, 
146 
in  proteid  metabolism  on  meat- 
fat  diet,  145 
of  proteid,  127,  128 
specific,  of  fat,  144 
of  foodstuffs,   133 
of  proteid,  126,   140 


Egg,  hen's,  heat  production  in,  193, 

i94_ 
Electricity,  33 

Emaciation  in  diabetes,   234 
Energy,  33 
cost  of,  299 
for  development,  193 
mechanical,   33 

production  of,  by  body,  fats  and 
carbohydrates  as  fuel  for,  167 
ontogenetic,  193 
potential,  33 

requirements    in    performance    of 
same    amount    of    mechanical 
work,  171 
in  starvation,  60 
source  of,  on  earth,  33 
value  of  proteid  in  diabetes,  237 
Epidermis,   nitrogen  in,   21 
Equilibrium,  carbon,   loi 
nitrogen,  20,  99,  100,  loi 

after  ingestion  of  carbohydrates, 

154,  155 
low    level    of,    in    normal    and 
undernutrition,  157 
Erythrocytes,   effect  of  high  altitude 

on,  221 
Exophthalmic  goiter,  metabolism  in, 

223 
Experimental  pancreas  diabetes,  226 


Fasting,  52.     See  also  Starvation. 
Fat   and    carbohydrates   interchange- 
able in  nutrition,  35 
as  fuel  for  production  of  mechani- 
cal energy  by  body,  167 
content,  influence  of,   on  length  of 
life  in  starvation,  68 
on  proteid  metabolism  in  star- 
vation, 68 
of    animal,    proteid    metabolism 
in  starvation  as  influenced  by,66 


320 


INDEX  OF  SUBJECTS. 


Fat  content  of  milk,  199,  200,  201 
action  of  fasting  on,    199 
conversion   of   carbohydrates   into, 

150,  151,  152 
effect  of,  on  metabolism,  87 
influence  on  meat  feces,  47 

on  metabolism,  87 
ingestion,  influence  of,  142 
on   nitrogen   retention,   145 
man,  metabolism  of  a,  effect  of  work, 
•     temperature,    and    humidity   on, 

94.  164 
metabolism,  absence  of  secondary 
dynamic  action   in,   on   meat- 
fat  diet,  146 
as  source  of  sugar   in   diabetes, 

230,  231,  233 
in  starvation,  73 
production  of,  from  proteid,  120 
quantity  of  proteid  metabolism  in 
starvation    depends    on    amount 
of,  66 
specific  dynamic  action  of,    144 
Fatal  ratio  in  diabetes,  241 
Fatty  degeneration  in  fevers,  266 

of  proteid,  246,  247 
Feces,  45 

amount  excreted,  49 

bone,  45 

bread  particles  in,  49 

collection   of,   for  given   period   of 

nutrition,  45 
composition  of,  on  different  diets, 

50 
heat  value  of,  36,  37,  51 
legumes  in,  49 
meat,  46,  47 

influence  of  bread  on,  47 
of  fat  on,  47 
of  sugar  on,  47 
milk,  46 

nitrogen  in,  21,  47 
normal,  50 

potato  particles  in,  49 
sources  of,  47 
starch  particles  in,  49 
starvation,  46,  47 
Fever,  aseptic,  249 
diet  in,  261 
etiology  of,  266 
fatty  degeneration  in,  266 
increase  of  purin  bases  in  urine  in, 

267,  268 
infectious,   249 

metabolism  in,  253 

toxic   destruction    of    body    pro- 
teid in,  258 
insensible  perspiration  in,  257 


Fever,  metabolism  in,  249 
effect  of  cold  on,  2 58 
of  heat  on,  257 
of  muscular  work  on,  25S 
milk  diet  in,  261 
neurogenic,  249,  252 
parenchymatous    degeneration    in, 

266 
physiological,   249 
toxic,  metabolism  in,  253 
typhoid,  diet  high  in  carbohydrate 
in,  264 
in  proteid  in,  263 
increase  of  purin  bodies  in  urine 

in,  268 
metabolism  in,  259,  262,  263,  264 
Food,  definition  of,  98,  177 

materials,  composition  of,  300-308 
proportion    of,    in    making    up    a 

ration,    177,    178 
proteid,  influence  of,  98 
requirement      during      period      of 

growth,  193 
statistics,  municipal,  188 
value  of  alcohol,  191 
Foodstuffs,    specific    dynamic  action 

of,  133 
Formilase,  294 


Gastric  juice  in  starvation,  69 
Gelatin  in  starvation,  57 

value  of,  in  metabolism,  102 
Gland,  thyroid,  effect  on  metabolism, 

222 
Glands  in  starvation,  69 
Globulin  in  blood  in  starvation,  70 
Glycocoll   production   after   ingesting 
proteid,  114 
and    nitrogen    elimination    con- 
stant ratio  between,  in  starva- 
tion,   65 
Glycogen,  148,  149 

distribution  of,  148 

in  diabetes,    240 

of  animal  in  starvation,   71 
Glycolaldehyde,   231 
Glycosuria,  alimentary,  226,  228 

phlorhizin,  226,  227,  228 
Goiter,  exophthalmic,  metabolism  in, 

223 
Gout,  270,  282 

diet  in,  287 

predisposing  causes,  283 

tolerance  for  purin  bodies  in,  286 
Growth  of  suckling  pigs,  208,  209 

period  of,  food  requirement  during, 
193 


INDEX  OF  SUBJECTS. 


321 


Growth,    rapidity    of,  and   longevity, 
relation  between,  211 

Guanin,  270,  271 

conversion  of,  into  uric  acid,  274 
metabolism  of,  intra-vitam,  276 


Hair,  nitrogen  in,  21 
Heat,  33,  34 

animal,  31 

effect  of,   on  metabolism  in  fever, 

258 
from    metabolism,    comparison    of, 
with  heat  actually  produced,  41 
loss  b}'  conduction  and  radiation,  83 
distribution  of,  after  meat  inges- 
tion, 131 
manner  of,  influence  of  temper- 
ature on,  89,  90 
paths  of,  83 

vary  with  temperature  of  envi- 
ronment, 83 
production  in  hen's  egg,  193,  194 

in  resting  animals,  81 
puncture  of  corpora  striata,  252 
regulation,  effect  of  clothes  on,  96 
requirement,  minimal,  130 
value  of  foodstuffs,  40 
of  feces,  36,  37,  51 
of  metabolism,  34 
Hemoglobin  in  starvation,  70 

increase  of,  at  high  altitude,  222 
Hen's  egg,  heat  production  in,   193, 

194 
High  altitude,  effect  on  metabolism, 
217,  218 
red-blood  cells,  221 
increase  of  hemoglobin  at,  222 
metabolism  at,  216 
Hippuric  acid  in  urine  in  starvation, 
64 
after  meat  ingestion,  114 
Hospital  dietaries,  188 
Humidity  and  temperature,  influence 
of,  on  metabolism  of  fat  man,  94, 
164 
effect  of,  on  metabolism,  88,  89 
Hunger,  52.     See  also  Starvation. 

specific  nitrogen,  156 
Hyperarterialization  of  blood,  30 
Hyperthermia,  249 
Hypoxanthin,   270,  271 
effect  on  uric  acid,  272 
in  muscle,  281,  282 


Ichthyosis   hystrix,   metabolism   in, 
250 

21 


Infectious  fever,   249 

fevers,  metabolism  in,  253 

toxic  destruction  of  body  proteid 
in,  258 
Insensible  perspiration,   17 
in  fever,  257 


Kynurenic  acid  in  urine,  117 


Lactalase,  294 

Lactic  acid,  conversion  of,  into  dex- 
trose, 232 
in  urine  after  bloodletting,  214 

after  phosphorus-poisoning,  247 
La  piqure,  225,  226 
Law,  Flourens's,  of  longevity,  211 

of  skin  area,  82,  295 
Legumes  in  feces,  49 
Leucin,    conversion   of,  into    acetone 

and  lactic  acid,  231,  232 
Leucyl-glycyl-glycin,  293 
Leukocythemia,    metabolism   in,    214 
Levulose  in  diabetes,  243 
Life,  length  of,  in  starvation,  65 

influence  of  fat  content  on,  68 


Magnetism,  t^t, 
Maintenance   diet,    125 
Meat  feces,  46,  47 

influence  of  bread  on,   47 
of  fat  on,  47 
of  sugar  on,  47 
influence    of    ingesting    increasing 

quantities  of,  loi 
proteid,  amount  of  nitrogen  in,  22 
Mechanical   energ\',   33 

production  of,  by  body,  fats  and 
carbohydrates  as  fuel  for,  167 
work,    carbon    dioxid    elimination 
from,  170 
effect  of,  on  metabolism,  160,  161 
on  nitrogen  metabolism,  165 
on  proteid  metabolism,   165 
energy  requirements  in  perform- 
ance of  same  amount  of,  171 
Meconium,  46 
Metabolism,   19 

after  meat  ingestion,  106 

variation  in,  108,  109 
proteid  ingestion  in  excess,  124 
influence    of    external    tem- 
perature on,   129 
and  diabetic  metabolism,  compari- 
son of,  236 
at  high  altitudes,  216 


322 


INDEX  OF   SUBJECTS. 


Metabolism,   carbohydrate,    influence 
of     d-glucuronic    acid     and 
pentoses  on,  244 
of  pentoses  on,  244 
cells  in,  42 

dav  and  night,  in  starvation,  73,  74 
diabetic,   and   normal    metabolism, 

comparison  of,  236 
dynamic  action  of,  41 
fat,  absence  of  secondary  dynamic 
action  in,  on  meat-fat  diet,  146 
as  source  of  sugar  in  diabetes, 

230,  231,  233 
in  starvation,   73 
gelatin  in,  102 
general  review,  288 
heat  from,  comparison  of,  with  heat 
actually  produced,  41 
value  of,  34 
in  anemia,  212 
in  boyhood,  146 
in  carcinoma,  258,  260 
in  croupous  pneumonia,   260 
in  diabetes,  225 
in  exophthalmic  goiter,  223 
in   fat   man,    influence   of   temper- 
ature and  humidity  on,  94 
in  fever,  24Q 

effect  of  cold  on,  258 
of  heat  on,  257 
of  muscular  work  on,  258 
in  ichthyosis  hystrix,  250 
in  infectious  fevers,   253 
in  Icukocythemia,  214 
in  myxedema,  223,  224 
in  phosphorus-poisoning,  246,  247, 

248 
in  pneumonia,  265 
in  starvation,  24,  58,  59,  60 

effect  of  temperature  on,  91 
in  toxic  fevers,  253 
in  tuberculosis,  260 
in     typhoid   fever,    259,    262,    263, 

264 
influence  of  alcohol  on,  190,  191 
of  cane  sugar  on,  150 
of  climate  on,  97 
of  clothes  on,  96 
of  cold  baths  on,  92,  93 
of  cold  on,  83 
of  dampness  on,  88 
of  fat  on.  87 

of  high  altitude  on,  217,  218 
of  humidity  on,  88,  89 
of  mechanical  work  on,  160,   161 
of  moisture  on,  89 
of  mountain  climbing  on,  173 
of  removal  of  ovaries  on,  222 


Metabolism,  influence  of  temperature 
on,  78,  86,  87 
laws  governing,  130 
of  thyroid   gland  on,   222 
of  training  on,  174,  175 
of  wind  on,  92,  93,  94 
on  castration,  222 
intermediate,  of  proteid,   114 
manner  of,  29,  288 
nitrogen,  effect  of  mechanical  work 
on,  165 
in  pneumonia,  265 
in  jjregnancy,  195,  196 
in   starvation   in   dogs,   influence 

of  work  on,  72 
of  animals  in  starvation,  57 
of  children,  205,  206 
of  fat  man,  effect  of  work,  temper- 
ature, and  humidity  on,  164 
of  guanin  intra-vitam,  276 
proteid,  124 

before  and  after  pregnancy,  195, 

197 
effect    of    copious    drinking    of 
water  on,    105 
of  diabetes  on,   235 
of  external  temperature  on,  128 
of  mechanical  work  on,  165 
of  muscle  work  on,   29 
in  starvation,  53,  57 

as  influenced  by  fat  content  of 

animal,  66 
in  dogs,  effect  of  work  on,  72 
influence  of  fat  content  on,  68 
quantity  of  depends  on  amount 
of  fat,  66 
secondary     dynamic     action     in, 

on  meat-fat  diet,  145 
susceptibility  of,  to  sudden  with- 
drawal of  carbohydrates,  154 
three  stages  of,   127 
purin,  270 

effect  of  alcohol  on,  283 
integral  factors  of,  277,  278 
quantity  of  oxygen  needed  in,  127 
respiration  and,  30 
theories  of,  288 
Milk,  absorption  of  energy-containing 
constituents  of,  203 
ash   of,    percentage   absorption   of, 

203 
calories  in,  percentage  distribution 

of,  204 
calorific  value  of,  205 
composition    of,    influence    of    diet 

on,  ig8,  200 
diet  in  fevers,  261 
results  of,   190 


INDEX  OF  SUBJECTS. 


323 


Milk,  fat  content  of,  199,  200,  201 
action  of  fasting  on,  199 

feces,  46 

milk  sugar  content  of,  200 

modified,  190,  205 

percentage  composition  of,  203 

production   of,    influence   of   nutri- 
tion on,   198 

secretion  in  starvation,  70 

sugar  content  of  milk,  200 

top,   205 
Minimal  heat  requirement,  130 
Modified  milk,   190,  205 
Moisture,  effect  of,  on  metabolism,  89 
Mountain  climbing,  effect  on  metabo- 
lism,  173 

sickness,  221 
Municipal  food  statistics,  188 
Muscle,  hypoxanthin  in,  281,   282 

work,  effect  on  proteid  metabolism, 
29 
Muscular  work,  effect  on  metabolism 

in  fever,  258 
Myxedema  metabolism  in,  223,  224 


Nexjkogenic  fever,  249,  252 
Nitrogen,     ammonia,     in     urine,     in 
starvation,  63 
amount  of,  in  meat  proteid,  22 
creatinin-,  in  urine,  118 
elimination  after  ingesting  proteid, 
114 
and    dextrose    production,    con- 
stant   ratio   between,    in    star- 
vation, 64 
and    glycocoll    production,    con- 
stant   ratio    between,    in    star- 
vation, 65 
epicritical,  in  croupous  pneumo- 
nia, 260 
epidermis  and,   21 
equilibrium,  99,  100,  loi 

after  ingestion  of  carbohydrates, 

154,  15s 
low    level    of,    in    normal    and 
undernutrition,  157 
excretion    before    and    after    meat 
ingestion  in  diabetes,  iii 
effect  of  temperature  on,  86 
in  starvation,  61,  62 
gas,  20 
hair  and,  21 
hunger,  specific,   156 
in  feces,  47 
in  urine,  20,  21 

and    sugar    elimination    in    dia- 
betes, relation  between,  228,229 


Nitrogen  in  urine,  in  starvation,  73,  74 
metabolism,    effect    of    mechanical 
work  on,  165 
in  pneumonia,  265 
in  pregnancy,  195,  196 
in   starvation  in   dogs,   influence 

of  work  on,  72 
of  animals  in  starvation,  57 
of  feces,  21 

purin,  in  animal  tissues,  281 
ration  of,  to  carbon,  in  urine,  36 
retention,  influence  of  fat  ingestion 

on,  145 
urea,  in  urine,  in  starvation,  63 
Nitrogenous  equilibrium,  20 
Normal  feces,  50 
Nuclease,  275 
Nucleoproteids,     products     obtained 

from,  271 
Nutrition,    influence    of,    on    produc- 
tion of  milk,   198 
Nutrose,  effect  of,  in  depancreatized 
dog,  230 


Ontogenetic  energy,  193 
Opium  in  diabetes,   242 
Organized  proteid,  55 
Ovaries,   removal  of,   effect    on    me- 
tabolism, 222 
Oxygen,  absorption  of,  in  starvation, 

5^  .       • 

increased  requirement  for,  m  preg- 
nancy, 194,  195 
quantity  needed,  in  metabolism,  27 
volume  inspired,  relation  to  volume 
of  carbon  dioxid  expired,  27 


Parenchymatous  degeneration  in 
fevers,  266 

Pentoses,  influence  of,  on  carbohy- 
drate metabolism,  244 

Pentosuria,  245 

Pepsinogen  in  starvation,  69 

Peptids,  293 

Perspiration,  insensible,  amount  of,  17 
in  fever,    257 

Phenylalanin  in  alcaptonuria,  116 

Phlorhizin  glycosuria,  226,  227,  228 

Phosphoric  acid  in  urine  in  starva- 
tion, 62 

Phosphorus-poisoning,  metabolism  in, 
246,  247,  248 

Physical  regulation  of  temperature, 
80,  84 

Physiological  fever,  249 

Piqflre,  225,  226 


324 


INDEX  OF  SUBJECTS. 


Plasma,  blood-,  in  starvation,  70 
Pneumonia,  croupous,  epicritical  nitro- 
gen elimination  in,  260 
metabolism  in,  260 
metabolism  in,  265 
nitrogen  metabolism  in,  265 
Poisoning,   phosphorus-,    metabolism 

in,  246,  247,  248 
Potato  particles  in  feces,  49 
Potential  energ)',  ^^ 
Pregnancy,   diet  in,    195 

increased   requirement   for   ox}gen 

in,  194,  195 
nitrogen  metabolism  in,  195,  196 
proteid     metabolism     before     and 
after,  195,  197 
Premortal  rise  in  star\'ation,  61,  66 
Pressure  of  atmosphere,  216 
Proteid,  amount  required,  in  making 
up  a  ration,  178,  181 
body,  toxic  destruction  of,  in  infec- 
tious fevers,  258 
calorific  value  of,  38 
circulating,  55 

in  starvation,  55,  56 
composition  of,  289,  290 
cost  of,   299 
deposit,  159 

dextrose  from,  in  diabetes,  238 
diet  high  in,  in  typhoid  fever,  263 
energy  value  of,  35 

in  diabetes,  237 
fatty  degeneration  of,   246,  247 
food,  influence  of,  98 
glycocoll    production    after    ingest- 
ing, 114 
ingestion,    carbon    retention    after, 
122,  123 
in  excess,  metabolism  after,  124 
metabolism    after,    influence    of 
external  temperature  on,  129 
intermediate  metabolism  of,   114 
meat,  amount  of  nitrogen  in,  22 
metabolism,  124 

before  and  after  pregnancy,  195, 

197 
in  star\-ation,  53,  57 

as  influenced  by  fat  content  of 

animal,  66 
influence  of  fat  content  on,  68 

of  work  on,  72 
quantity      of,      depends      on 
amount  of  fat,  66 
influence  of  copious  drinking  of 
water  on,   105 
of  diabetes  on,  235 
of    external    temperature    on, 


Proteid,    metaboHsm,     influence     of 
mechanical  work  on,  165 
of  muscle  work  on,   29 
secondary    dynamic     action     in, 

on   meat-fat  diet,    145 
susceptibility  of,  to  sudden  with- 
drawal  of  carbohydrates,    154 
three  stages  of,   127 
nitrogen    elimination    after   ingest- 
ing, 114 
organized,  55 

production  of  fat  from,   120 
regeneration  of  amino  bodies  into, 

291 
secondary  dynamic  action  of,  127, 

128 
specific  dynamic  action  of,  126,  140 
sugar  from,  in  diabetes,  no 
Proteolytic    cleavage    products,    56 
Puncture,    heat,    of    corpora   striata, 

252 
Purin,   270 
bases,    271 
bodies,  271 

endogenous,    277 
exogenous,   277 
in  urine  in  starvation,  63 
increase   of,    in   urine   in    fever, 
267,  268 
in  tuberculosis,  268 
in  typhoid  fever,  268 
relations   between,    270 
tolerance   for,    in   gout,    286 
metabolism,  270 

effect  of  alcohol   on,    283 
integral  factors  of,  277,  278 
nitrogen   in   animal   tissues,   281 
Purin-free   diet,    277 
Pyramidin  bases,  272 


Quotient,  respiratory,  loi 


Red  blood-cells,   efifect  of  high   alti- 
tude on,  221 
Regulation  of  temperature,    78 
chemical,  80,  83 

action  of,  in  dog,  85 
in    guinea-pig,    84 
effect  of  curare  on,  82 
physical,  80,  84 
Respiration,    carbon    dioxid   elimina- 
tion in,  30 
metabolism  and,  30 
Respiratory  cjuotient,  27,  loi 
Rhamnose  in  diabetes,  245 
Rubner's  standard  values,  40 


INDEX  OF  SUBJECTS. 


325 


Sickness,   mountain,    221 
Skin  area,  law  of,  82,  295 
Specific  dynamic  action,  133 
Specific  nitrogen  hunger,  156 
Standard  dietaries,  187,  188 

values,   Rubner's,  40 
Starch  particles  in  feces,  49 
Starvation,  52 

absorption  of  oxygen  and  elimina- 
tion of  carbon  dioxid  in,  58 
acetonuria  in,  63 

action  of,  on  fat  content  of  milk,  199 
albuminuria  in,  63 
ammonia   excretion   in,   63 

nitrogen   in   urine   in,    63 
bile  in,  69 
blood  in,  70 
blood-corpuscles  in,   70 
blood-plasma   in,    70 
/3-oxybutyric  acid  in  urine  in,  63 
chlorin  in  urine  in,   63 
circulating   proteid  in,   55,    56 
constant    ratio    between    dextrose 
production  and  nitrogen  elimina- 
tion in,  64 
day  and  night  excretion  of  carbon 
dioxid   in,    74 
metabolism  in,  73,   74 
death  from,  cause  of,   67 
definition  of,   52 
dextrose   in   blood   in,    70 

urine  in,  63 
diabetes,   226 

energy  requirements  in,  60 
fat  metabolism  in,   73 
feces,  46,  47 
gastric  juice  in,   69 
gelatin   in,   57 
glands   in,   69 
globulin  in  blood  in,  70' 
glycocoll   production   and   nitrogen 
elimination     in,     constant     ratio 
between,    65 
glycogen  of  animal  in,  71 
hemoglobin  in,  70 
hippuric  acid  in  urine  in,   64 
in    dogs,    nitrogen    metabolism  in, 
influence  of  work  on,   72 
proteid  metabolism  in,    effect  of 
work  on,   72 
influence  of  work  on,   72 

on   spirits,    53 
length   of  life   in,    65 

influence  of  fat  content  on,  68 
loss  of  weight  in,  67 

of  different  organs,  69 
metabolism  in,  24,  58,  59,  60 
effect    of   temperature   on,    91 


Starvation,    milk   secretion   in,    70 
nitrogen   excretion   in,    61,  62 
in  urine  in,  73,  74 
metabolism  of  animals  in,   57 
organs    attacked    in,    69 
pepsinogen   in,   69 
phosphoric  acid  in  urine  in,  62 
premortal  rise  in,   61,   66 
proteid  metabolism  in,  53,  57 

as  influenced  by  fat  content  of 
animal,  66 
purin   bodies   in   urine   in,    63 
quantity  of  proteid  metabolism  in, 

depends  on  amount  of  fat,  66 
relations   between    weight   of  indi- 
vidual   and    calorific   production 
in,  59  _ 
sulphur  in  urine  in,  61 
temperature  in,  74-77 
urea    elimination    in,    attributable 
to  previous  diet,  55 
influence  of  previous  diet  on,  54 
nitrogen  in  urine  in,   63 
urine  analysis  in,  62 
water,  52 
Sugar,  cane,  influence  on  metabolism, 

150 
colloid,  227 

influence  on  meat  feces,  47 
milk,    in   milk,    200 
production    of,     from    proteid    in 
diabetes,   no 
Sulphur  in  urine  in  starvation,  61 
Sunstroke,    249 


Tea,   stimulating  action  of,   170 
Temperature  and  humidity,  influence 
of,  on  metabolism  of  fat  man,  94 
chemical  regulation  of,  80,  83 
action  of,  in  dog,  85 
in  guinea-pig,  84 
critical,  84 

effect  of,  on  manner  of  heat  loss, 
89,  90 
on   metabolism,    78,    86,    87 
in  starvation,  91 
laws   governing,    130 
of  fat  man,  164 
on   nitrogen   excretion,    86 
external,   influence   of,    on    metab- 
olism   after    proteid    inges- 
tion, 129 
on  proteid  metabolism,   128 
in  starvation,  74-77 
physical  regulation  of,  80,   84 
regulation  of,  78 

effect  of  curare  on,  82 


326 


INDEX  OF  SUBJECTS. 


Theobromin,   273 

Theophyllin,   273 

Theories  of  metabolism,  288 

Theon%   compensation,    125,    133 

Thyroid  gland,  effect  on  metabolism, 

222 
Thyroidectomy,     clonic     convulsions 

after,  224 
Tissue,  crushed,  power  of,  to  destroy 
uric  acid,   274 

purin  nitrogen  in,  281 
Top  milk,  205 

Toxic  fevers,  metabolism  in,  253 
Training,   effect   of,   on   metabolism, 

'7-^•   ^75       .  .         .     ,     , 

Tuberculosis,  mcrease  of  purm  bod- 
ies  in    urine   in,    268 
metabolism  in,  260 
Typhoid  fever,  diet  high  in  carbohy- 
drate  in,    264 
in  proteid  in,  263 
increase  of  purin  bodies  in  urine 

in,  2 68 
metabolism  in,  259,  262,  263,  264 
Tyrosin  in  alcaptonuria,   116 


Urea,  22 

conversion  of  uric  acid  into,  275 
elimination    in    starvation    attribu- 
table to  previous  diet,  55 
influence  of  previous  diet  on,  54 
nitrogen  in  urine  in  starvation,  63 
Uric  acid,  270,   271 

conversion  of  adenin  into,  274 
guanin  into,  274 
into  urea,  275 
effect  of  hypoxanthin  on,  272 
elimination,  effect  of  adenin  on, 

272 
endogenous,  277 
excretion,  endogenous,  constancy 

of,  278 
exogenous,  277 

power     of     crushed     tissue     to 
destroy,  274 
Urine,  allantoin  in,  272,  275,  276 
ammonia  in,  in  starvation,  63 
nitrogen  in,  in  starvation,  63 
analysis  in  starvation,  62 
^-oxy butyric  acid  in,  in  starvation, 

caloric  value  of,  36 
chlorin  in,  in  starvation,  63 
creatin  in,  117,  118 
creatinin  in,  117 


Urine,  dextrose  in,  in  starvation,  63 
hippuric  acid  in,  in  starvation,  64 
kynurcnic  acid  in,  117 
lactic  acid  in,  after  bloodletting,  214 
nitrogen   in,    20,    21 

and    sugar    elimination,    relation 
between,  in  diabetes,  228,  229 
in  starvation,  61,  62,  73,  74 
phosphoric  acid  in,  in  starvation,  62 
purin  bodies  in,  in  starvation,  63 
increase  of,  in  fever,  267,  268 
in  tuberculosis,  268 
in   typhoid   fever,    268 
ratio  of  nitrogen  to  carbon  in,  36 
sulphur  in,  in  starvation,  61 
urea  nitrogen  in,  in  starvation,  63 


Vegetarianism,  Graham  system  of, 
180 


Water,  copious  drinking  of,  action  of, 
106 
effect   on   proteid   metabolism, 

105 
hunger,   52 
Weight,  loss  of,  in  starvation,  67 

of  different  organs,  in  starvation, 
69 
Wind,   influence  of,   on   metabolism, 

92,  93.  94 
Work,  influence  of,  on  metabolism  of 
fat  man,  164 
on  nitrogen  metabolism  in  fasting 

dogs,   72 
on  proteid  metabolism  in  fasting 

dogs,   72 
on  starvation,  72 
mechanical,  carbon  dioxid  elimina- 
tion from,  170 
effect  of,  on  metabolism,  160,  161 
on  nitrogen  metabolism,   165 
on  proteid  metabolism,   165 
energy      requirements     in      per- 
formance of  same  amount  of, 
171 
muscular,  effect  on  metabolism  in 
fever,   258 


Xanthin,  270,  271 


Yeast  in  diabetes,   243 


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Prevalent  Diseases  of  the  Eye.  By  Samuel  Theobald,  M.  D., 
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EYE,  EAR,   NOSE,  AND    THROAT.  5 

American  Text-Book  qf 
Eye,  Ear,  Nose,  and  Throat 

American  Text=Book  of  Diseases  of  the  Eye,  Ear,  Nose,  and 
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Hyde  and  Montgomery's 
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Haab  and  deSchweinitz's 
Operative  Ophthalmology 

Atlas  and  Epitome  of  Operative  Ophthalmology.  By  Dr.  O. 
H.A.AB,  of  Zurich.  PLdited,  with  additions,  by  G.  ¥..  deSchweinitz, 
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the  fact  that  mere  verbal  descriptions  are  frequently  insufficient  to  give  a  clear 
idea  of  operative  procedures,  Dr.  Haab  has  taken  particular  care  to  illustrate 
plainly  the  different  parts  of  the   operations. 

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■  The  descriptiuns  of  the  >».rious  operations  are  so  clear  and  full  that  the  volume  can  well 
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DISEASES    OF   THE  EYE. 


Haab  and  DeSchweinitz's 
External  Diseases  qf  the  Eye 


Atlas  and  Epitome  of  External  Diseases  of  the  Eye.     By  Dr.  O. 

Haab,  of  Zurich.  Edited,  with  additions,  by  G.  E.  deSchweinitz, 
M.  D.,  Professor  of  Ophthalmolog}-,  University  of  Pennsylvania.  With 
98  colored  illustrations  on  48  lithographic  plates  and  232  pages  of 
text.     Cloth,  33. 00  net.     /;/  Saunders  Hand-Atlas  Series. 

SECOND   REVISED    EDITION— RECENTLY   ISSUED 

Conditions  attending  diseases  of  the  external  eye,  which  are  often  so  complicated, 
have  probably  never  been  more  clearly  and  comprehensively  expounded  than  in 
the  forelying  work,  in  which  the  pictorial  most  happily  supplements  the  verbal 
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Ophthalmoscopy 


Atlas  and  Epitome  of  Ophthalmoscopy  and  Ophthalmoscopic 
Diagnosis.  By  Dr.  O.  Haab,  of  Ziirich.  Fro;n  the  Third  Revised 
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The  great  value  of  Prof.  Haab's  Atlas  of  Ophthalmoscopy  and  Ophthalmo- 
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translation.  Not  only  is  the  student  made  acquainted  with  carefully  prepared 
ophthalmoscopic  drawings  done  into  well-executed  lithographs  of  the  most  im- 
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The  Lancet,  London 

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NOSE,    THROAT,   AND   EAR. 


Gradle*s 
Nose,  Pharynx,  and  Ear 

Diseases  of  the  Nose,  Pharynx,  and  Ear.  By  Henry  Gradle, 
M.  D.,  Professor  of  Ophthalmology  and  Otology,  Northwestern  Uni- 
versity Medical  School,  Chicago.  Handsome  octavo  of  547  pages, 
illustrated,  including  two  full-page  plates  in  colors.     Cloth,  ^3.50  net. 

INCLUDING  TOPOGRAPHIC  ANATOMY 

This  volume  presents  diseases  of  the  Nose,  Pharynx,  and  Ear  as  the  author 
has  seen  them  during  an  experience  of  nearly  twenty-five  years.  In  it  are 
answered  in  detail  those  questions  regarding  the  course  and  outcome  of  diseases 
which  cause  the  less  experienced  observer  the  most  anxiety  in  an  individual  case. 
Topographic  anatomy  has  been  accorded  liberal  space. 

Pennsylvania  Medical  Journal 

"This  is  the  most  practical  volume  on  the  nose,  pharynx,  and  ear  that  has  appeared 
recently.  ...  It  is  exactly  what  the  less  experienced  observer  needs,  as  it  avoids  the  confusion 
incident  to  a  categorical  statement  of  everv^body's  opinion." 

Kyle*s 
Diseases  of  Nose  am)  Throat 


Diseases  of  the  Nose  and  Throat.  By  D.  Braden  Kyle,  M.  D,, 
Professor  of  Laryngology  in  the  Jefferson  Medical  College,  Phila- 
delphia; Consulting  Laryngologist,  Rhinologist,  and  Otologist,  St. 
Agnes'  Hospital  Octavo,  669  pages;  over  184  illustrations,  and  26 
lithographic   plates   in  colors.     Cloth,  ;^4.oo  net. 

RECENTLY   ISSUED— THIRD   REVISED   EDITION 

Three  large  editions  of  this  excellent  work  fully  testify  to  its  practical 
value.  In  this  edition  the  author  has  revised  the  text  thoroughly,  bringing 
it  absolutely  down  to  date.  With  the  practical  purpose  of  the  book  in  mind,  ex- 
tended consideration  has  been  given  to  treatment,  each  disease  being  considered  in 
full,  and  definite  courses  being  laid  down  to  meet  special  conditions  and  symptoms. 

Dudley  S.  Reynolds.  M.  D.. 

Formerly  Professor  of  Ophthalmology  and  Otology,  Hospital  College  of  Medicine,  Louisville. 

"  It  is  an  important  addition  to  the  text-books  now  in  use,  and  is  better  adapted  to  the  uses 
of  the  student  than  any  other  work  with  which  I  am  famihar.  I  shall  be  pleased  to  commend 
Dr.  Kyle's  work  as  the  best  text-book." 


SAUNDERS'  BOOKS   ON 


Griinwald  and  Grayson's 
Diseases  of  the  Larynx 

Atlas  and  Epitome  of  Diseases  of  tlie  Larynx.  By  Dr.  L.  Grun- 
WALH,  of  iMunich.  Edited,  with  additions,  by  Charles  P.  Grayson, 
M.l)..  Clinical  Professor  of  Laryngology  and  Rhinology,  University 
of  Pennsylvania.  With  107  colored  figures  on  4.].  plates,  25  text-cuts, 
and  103  pages  of  text.  Cloth,  $2.50  net.  ///  Saunders  Hand-Atlas 
Series. 

British  Medical  Journal 

"  Excels  evervtliiiig  we  have  hitherto  seen  in  the  way  of  colored  illustrations  of  diseases  of 
the  larynx.  .  .  .  Not  only  valuable  for  the  teaching  of  laryngology,  it  will  prove  of  the  greatest 
help  to  those  who  are  perfecting  themselves  by  private  study." 

American  Text-Book  of 

Genito-Urinary,  Syphilis,  Skin 

American  Text=book  of  Genito=Urinary  Diseases,  Syphilis,  and 
Diseases  of  the  Skin.  Edited  by  L.  Bolton  Baxgs,  M.  D.,  late  Prof. 
of  Genito-Urinary  Surger\',  University  and  Bellevue  Hospital  Medical 
College,  New  York;  and  W.  A.  Hardaw.w.  M.  D.,  Professor  of  Diseases 
of  the  Skin,  Missouri  Medical  College.  Imperial  octavo,  1229  pages, 
with  300  engravings,  20  colored  plates.     Cloth,  $7.00  net. 

Journal  of  the  American  Medical  Association 

"This  voluminous  work  is  thoroughly  up-to-date,  and  the  chapters  on  genito-urinary  dis- 
eases are  especially  valuable.  The  illustrations  are  fine  and  are  mostly  original.  The  section 
on  dermatology  is  concise  and  in  every  way  admirable." 

SennV 

Genito-Urinary  Tuberculosis 

Tuberculosis  of  the  Qenito=Urinary  Organs,  Male  and  Female. 

By  N.  Senx,  M.  D.,  Ph.  D.,  LL.D.,  Professor  of  Surgery  in  Rush  Med- 
ical College.     Octavo  of  317  pages,  illu.strated.     Cloth,  S3.00  net. 
British  Medical  Journal 

"  The  book  will  well  repay  perusal.  It  is  the  final  word,  as  our  knowledge  stands,  upon 
the  diseases  of  which  it  treats,  and  will  add  to  the  reputation  of  its  distinguished  author." 


DISEASES   OF   THE  SKIN. 


Mracek  and  Stelwagon's 
Diseases  of  the  Skin 

Atlas  and  Epitome  of  Diseases  of  the  Skin.  By  Prof.  Dr.  Franz 
Mracek,  of  Vienna.  Edited,  with  additions,  by  Henry  W.  Stelwagon, 
M.  D.,  Professor  of  Dermatology  in  the  Jefferson  Medical  College, 
Philadelphia.  With  yy  colored  plates,  50  half-tone  illustrations,  and 
280  pages  of  text.     In  Saunders'  Ha7id- Atlas  Series.  Clo.,  ;$4.oonet. 

RECENTLY   ISSUED— NEW  (2nd)  EDITION 

This  volume,  the  outcome  of  years  of  scientific  and  artistic  work,  contains, 
together  with  colored  plates  of  unusual  beauty,  numerous  illustrations  in  black, 
and  a  text  comprehending  the  entire  field  of  dermatology.  The  illustrations  are 
all  original  and  prepared  from  actual  cases  in  Mracek' s  clinic,  and  the  execution 
of  the  plates  is  superior  to  that  of  any,  even  the  most  expensive,  dermatologic 
atlas  hitherto  published. 

American  Jotirnal  of  the  Medical  Sciences 

' '  The  advantages  which  we  see  in  this  book  and  which  recommend  it  to  our  minds  are : 
First,  its  handiness ;  secondly,  the  plates,  which  are  excellent  as  regards  drawing,  color,  and  the 
diagnostic  points  which  they  bring  out." 

Mracek  and  Ban^s* 
Syphilis  and  Venereal 

Atlas    and    Epitome   of    Syphilis    and    the    Venereal    Diseases. 

By  Prof.  Dr.  Franz  Mracek,,  of  Vienna.  Edited,  with  additions,  by 
L.  Bolton  Bangs,  M.  D.,  late  Prof,  of  Genito-Urinary  Surger>%  Univer- 
sity and  Bellevue  Hospital  Medical  College,  Xew  York.  With  71 
colored  plates  and  122  pages  of  text.  Cloth,  S3. 50  net.  In  Saunders' 
Hand- Atlas  Scries. 

CONTAINING    71    COLORED    PLATES 

According  to  the  unanimous  opinion  of  numerous  authorities,  to  whom  the 
original  illustrations  of  this  book  were  presented,  they  surpass  in  beauty  anything 
of  the  kind  that  has  been  produced  in  this  field,  not  only  in  Germany,  but 
throughout  the  literature  of  the  world. 

Robert  L.  Dickinson,  M.  D., 

Aii  Editor  of  "  The  America7i  Text-Book  of  Obstetrics." 
"  The  book  that  appeals  instantly  to  me  for  the  strikingly  successful,  valuable,  and  graphic 
character  of  its  illustrations  is  the  'Atlas  of  Syphilis  and  the  Venereal  Diseases.'     I  know  of 
nothing  in  this  country  that  can  compare  with  it." 


S.4[^A'nE/^S'  BOOKS   ON 


Holland's  Medical 
Chemistry  and  Toxicology 

A  Text=Book  of  Medical  Chemistry  and  Toxicology.  Wy  James 
W.  Holland,  M.D.,  Professor  of  Medical  Chemistry  and  Toxicology, 
and  Dean,  Jefferson  Medical  College,  Philadelphia.  Octavo  of  592 
pages,  fully  illustrated.     Cloth,  S3.00  net. 

RECENTLY   ISSUED 

Dr.  Holland's  work  is  an  entirely  new  one,  and  is  based  on  his  thirty -five 
years'  practical  experience  in  teaching  chemistry  and  medicine.  Recognizing 
that  to  understand  physiologic  chemistry,  students  must  first  be  informed  upon 
points  not  referred  to  in  most  medical  text-books,  the  author  has  included  in  his 
work  the  latest  views  of  equilibrium  of  equations,  mass  action,  cryoscopy,  os- 
motic pressure,  dissociation  of  salts  into  ions,  effects  of  ionization  upon  electric 
conductivity,  and  the  relationship  between  purin  bodies,  uric  acid,  and  urea. 
More  space  is  given  to  toxicology  than  in  any    other  text-book  on  chemistry. 

American  Medicine 

"  Its  statements  are  clear  and  terse ;  its  illustrations  well  chosen  ;  its  development  logical, 
systematic,  and  comparatively  easy  to  follow.  .  .  .  We  heartily  commend  the  work." 


Grtinwald  and  Newcomb's 
Mouth,  Pharynx,  and  Nose 

Atlas  and  Epitome  of  Diseases  of  the  Mouth,  Pharynx,  and 
Nose.  By  Dr.  L.  Grunwald,  of  jMunich.  From  the  Second  Revised 
and  Enlarged  German  Edition.  Edited,  with  additions,  by  James  E. 
Newcomb,  M.  D.,  Instructor  in  Laryngology,  Cornell  University  Medical 
School.  With  102  illustrations  on  42  colored  lithographic  plates,  41 
te.xt-cuts,  and  219  pages  of  text.  Cloth,  ^3.00  net.  In  Saunders' 
Hand-Atlas  Series. 

INCLUDING   ANATOMY   AND    PHYSIOLOGY 

In  designing  this  atlas  the  needs  of  both  student  and  practitioner  were  kept 
constantlv  in  mind,  and  as  far  as  possible  typical  cases  of  the  various  diseases 
were  selected.  The  illustrations  are  described  in  the  text  in  exactly  the  same  way 
as  a  practised  examiner  would  demonstrate  the  objective  findings  to  his  class. 
The  illustrations  themselves  are  numerous  and  exceedingly  well  executed.  The 
editor  has  incorporated  his  own  valuable  experience,  and  has  also  included  exten- 
sive notes  on  the  use  of  the  active  principle  of  the  suprarenal  bodies. 

American  Medicine 

•'  Its  conciseness  without  sacrifice  of  clearness  and  thoroughness,  as  well  as  the  e.xcellence 
of  text  and  illustrations,  are  commendable." 


EYE,  EAR,  NOSE,  AND    THROAT.  13 

Jackson  on  the  Eye 

A  Manual  of  the  Diagnosis  and  Treatment  of  Diseases  of  tiie  Eye. 

By  Edward  Jackson,  A.  M.,  M.  D.,  Emeritus  Professor  of  Diseases  of 
the  Eye  in  the  Philadelphia  Polyclinic.  i2mo  volume  of  535  pages, 
with  178  beautiful  illustrations,  mostly  from  drawings  by  the  author. 
Cloth,  ^2.50  net. 

The  Medical  Record,  New  York 

"  It  is  truly  an  admirable  work.  .  .  .  Written  in  a  clear,  concise  manner,  it  bears  evidence 
of  the  author's  comprehensive  grasp  of  the  subject.  The  term  '  multum  in  parvo  '  is  an  appro- 
priate one  to  apply  to  this  work.  It  will  prove  of  value  to  all  who  are  interested  in  this  branch 
of  medicine." 


Grant  on  the 
Face,  Mouth,  and  Jaws 

A  Text=Book  of  the  Surgical  Principles  and  Surgical  Diseases  of 
the  Face,  Mouth,  and  Jaws.  For  Dental  Students.  By  H.  Horace 
Grant,  A.  M.,  M.  D.,  Professor  of  Surgery  and  of  Clinical  Surgery, 
Hospital  College  of  Medicine,  Louisville.  Octavo  of  231  pages,  with 
68  illustrations.     Cloth,  $2.'i,o  net. 

Annals  of  Surgery 

"  The  book  is  well  illustrated,  the  text  is  clear,  and  on  the  whole  it  serves  well  for  the 
purpose  for  which  it  is  intended." 

Friedrich  and  Curtis* 
Nose,  Larynx,  and  Ear 

Rhinology,  Laryngology,  and  Otology,  and  Their  Significance  in 
General  Medicine.  By  Dr.  E.  P.  Friedrich,  of  Leipzig.  Edited  by 
H.  Holbrook  Curtis,  M.D.,  Consulting  Surgeon  to  the  New  York 
Nose  and  Throat  Hospital.  Octavo  volume  of  350  pages.  Cloth. 
^2.50  net. 

Boston  Medical  and  Surgical  Journal 

"  This  task  he  has  performed  admirably,  and  has  given  both  to  the  general  practitioner  and 
to  the  specialist  a  book  for  collateral  reference  which  is  modern,  clear,  and  complete." 


14  SAi'XDERS'    BOOKS    OX 

O^den  on  the  Urine 


Clinical  Examination  of  Urine  and  Urinary  Diagnosis,  A  Clinical 
Guide  for  the  Use  of  Practitioners  and  Students  of  Medicine  and  Sur- 
gcrv.  By  J.  Bergen  Ogden,  M.  D.,  Late  Instructor  in  Chemistry, 
Harvard  University  Medical  School ;  Formerly  Assistant  in  Clinical 
Pathology,  Boston  City  Hospital.  Octavo,  418  pages,  54  illustrations, 
and  a  number  of  colored  plates.      Cloth.  $3.00  net. 

SECOND  REVISED  EDITION— RECENTLY  ISSUED 

In  this  edition  the  work  has  ijeen  Ijrought  absolutely  down  to  the  present  day. 
Important  chans^es  have  been  made  in  connection  with  the  determination  of  Urea, 
Uric  Acid,  and  Total  Nitrogen  ;  and  the  subjects  of  Crjoscopy  and  Beta-Oxybutyric 
Acid  have  been  given  a  place.  Special  attention  has  been  paid  to  diagnosis  by 
the  character  of  the  irrine,  the  diagnosis  of  diseases  of  the  kidneys  and  urinary 
passages  ;  an  enumeration  of  the  prominent  clinical  symptoms  of  each  disease  ; 
and  the  peculiarities  of  the  urine  in  certain  general  diseases. 

The  Lancet,  London 

"  We  consider  this  manual  to  have  been  well  compiled  ;  and  the  author's  own  experience, 
so  clearly  stated,  renders  the  volume  a  useful  one  both  for  study  and  reference." 

Vecki*s  Sexual  Impotence 


The  Pathology  and  Treatment  of  Sexual  Impotence.  By  Victor 
G.  Vecki,  M.  D.  From  the  Second  Revised  and  Enlarged  German 
Edition.      i2mo  volume  of  329  pages.     Cloth,  $2.00  net. 

THIRD   EDITION.  REVISED  AND  ENLARGED 

The  subject  of  impotence  has  but  seldom  been  treated  in  this  country  in  the 
truly  scientific  spirit  that  its  pre-eminent  importance  deserves,  and  this  volume  will 
come  to  many  as  a  revelation  of  the  possibilities  of  therapeutics  in  this  important 
field.  The  reading  part  of  the  English-speaking  medical  profession  has  passed 
judgment  on  this  monograph.  The  whole  subject  of  sexual  impotence  and  its 
treatment  is  discussed  by  the  author  in  an  exhaustive  and  thoroughly  scientific 
manner.  In  this  edition  the  book  has  been  thoroughly  revised,  and  new  matter 
has  been  added,  especially  to  the  portion  dealing  with  treatment. 

Johns  Hopkins  Hospital  Bulletin 

"  A  scientific  treatise  upon  an  important  and  much  neglected  subject.  .  .  .  The  treatment 
of  impotence  in  general  and  of  sexual  neurasthenia  is  discriminating  and  judicious." 


CHEMISTRY,   SKIN,   AND    VENEREAL    DISEASES.  15 

American  Pocket  Dictionary  ^""^^^^l^^^U^^^ 

The  American  Pocket  Medical  Dictionary.  Edited  by  W.  A. 
Newman  Borland,  M.  D.,  Assistant  Obstetrician  to  the  Hospital 
of  the  University  of  Pennsylvania.  Containing  the  pronunciation 
and  definition  of  the  principal  words  used  in  medicine  and  kindred 
sciences.  Flexible  leather,  with  gold  edges,  ;^i.oo  net ;  with  thumb 
index,  I1.25  net. 
James  W.  Holland,  M.  D., 

Professor  of  Medical  Chemistry  and  Toxicology,  and  Dean,  fefferson  Medical  College, 
Philadelphia, 

"  I  am  struck  at  once  with  admiration  at  the  compact  size  and  attractive  exterior.     I 
can  recommend  it  to  our  students  without  reserve." 

Stelwagon's  Essentials  of  Skin  ^"t?e„^^^1sS°" 

Essentials  of  Diseases  of  the  Skin.  By  Henry  W.  Stel- 
wagon,  M.  D.,  Ph.D.,  Professor  of  Dermatology  in  the  Jeffer- 
son Medical  College,  Philadelphia.  Post-octavo  of  276  pages, 
with  72  text-illustrations  and  8  plates.  Cloth,  ^i.oo  net.  In 
Saunders'  Question- Compend  Series. 
The  Medical  News 

"  In  line  with  our  present  knowledge  of  diseases  of  the  skin.  .   .   .  Continues  to  main- 
tain the  high  standard  of  excellence  for  which  these  question  compends  have  been  noted." 

Wolffs  Medical  Chemistry  ^^ReSSTssued"^ 

Essentials  of  Medical  Chemistry,  Organic  and  Inorganic. 
Containing  also  Questions  on  Medical  Physics,  Chemical  Physiol- 
ogy, Analytical  Processes,  Urinalysis,  and  Toxicology.  By  Law- 
rence Wolff,  M.  D.,  Late  Demonstrator  of  Chemistry,  Jefferson 
Medical  College.  Revised  by  Smith  Ely  Jelliffe,  M.  D.,  Ph.D., 
Professor  of  Pharmacognosy,  College  of  Pharmacy  of  the  City  of 
New  York.  Post-octavo  of  222  pages.  Cloth,  ^i.oo  net.  In 
Saunders'  Question-  Compend  Series. 
New  York  Medical  Journal 

"  The  author's  careful  and  well-studied  selection  of  the  necessary  requirements  of  the 
student  has  enabled  him  to  furnish  a  valuable  aid  to  the  student." 

Martin's  Minor  Surgery,  Bandaging,  and  the  Venereal 

Diseases  second  edition.  Revised 

Essentials  of  Minor  Surgery,  Bandaging,  and  Venereal 
Diseases.  By  Edward  Martin,  A.  M.,  M.  D.,  Professor  of  Clin- 
ical Surgery,  University  of  Pennsylvania,  etc.  Post-octavo,  166 
pages,  with  78  illustrations.  Cloth,  ^i.oo  net.  /;/  Saunders' 
Question-  Compend  Series. 
The  Mediced  News 

"  The  best  condensation  of  the  subjects  of  which  it  treats  yet  placed  before  the  pro- 
fession." 


,6  L'RIXE,  EVE,  EAR,  NOSE,  AND    THROAT. 


Wolfs  Examination  of   Urine 

A  Laisokatokv  Handbook  of  Physiologic  Chemistry  and 
Ukink-examination.  By  Charles  G.  L.Wolf,  M.  D.,  Instructor  in 
Physiologic  Chemistry,  Cornell  University  Medical  College,  New 
York.    1 2mo  volume  of  204  pages,  fully  illustrated.  Cloth,  ;^i.25  net. 

British  Medical  Journal 

■  1  hf  methods  of  examining  the  urine  are  very  fully  described,  and  there  are  at  the 
t.iiil  of  the  bi'ok   some   extensive   tables  drawn  up  to  assist  in  urinary  diagnosis." 

Jackson's  Essentials  of  Eye  Third  Revised  Edition 

E.SSENTIALS  OF  REFRACTION  AND  OF  DISEASES  OF  THE  EyE.       By 

Edward  Jackson,  A.  M.,  M.  D.,  FLmeritus  Professor  of  Diseases  of 
the  Eye,  Philadelphia  Polyclinic.  Post-octavo  of  261  pages,  82  illus- 
trations. Cloth,  :^ I. GO  net.  ///  Saunders'  Queshon-Covipend  Series. 
Johns  Hopkins  Hospital  Bulletin 

"  The  entire  ground  is  covered,  and  the  points  that  most  need  careful  elucidation 
are  made  clear  and  easy." 

Gleason's  Nose  and  Throat  Third  Edition,  Revised 

Essentials  of  Diseases  of  the  Nose  and  Throat.  By  E.  B. 
Gleason,  S.  B.,  M.  D.,  Clinical  Professor  of  Otology,  Medico- 
Chirurgical  College,  Philadelphia,  etc.  Post-octavo,  241  pages,  1 12 
illustrations.     Cloth,  Si. 00  net.     ///  Saunders'  Question  Compends, 

The  Lancet,  London 

"The  careful  description  which  is  given  of  the  various  procedures  would  be  sufficient 
to  enable  most  people  of  average  intelhgence  and  of  slight  anatomical  knowledge  to 
make  a  very  good  attempt  at  laryngoscopy." 

Gleason*s  Diseases  of  the  Ear  Third  Edition.  Revised 

E.SSENTIALS  OF  DisE.\sES  OF  THE  Ear.     By  E.  B.  Gleason,  S.  B., 
M.  D.,  Clinical  Professor  of  Otology,  Medico-Chirurgical  College, 
Phila.,  etc.     Post-octavo   volume  of  214  pages,  with    114  illustra- 
tions.    Cloth,  ;$ I. GO  net.      ///  Saunders'  Question-Conipend  Series. 
Bristol  Medico-Chirurgical  Journal 

"  We  know  of  no  other  small  work  on  ear  diseases  to  compare  with  this,  either  in 
freshness  of  style  or  completeness  of  information." 

Wilcox  on  Genito- Urinary  and  Venereal  Diseases    y%1^^ 

Essentials  of  Genito-Urinarv  and  Venereal  Diseases.  By 
Starling  S.  Wilco.x,  M.  D.,  Professor  of  Genito-Urinary  Diseases 
and  Syphilology,  Starling  Medical  College,  Columbus,  Ohio.  i2mo 
of  313  pages,  illustrated.    Cloth,  $i.GO  net.     Saunders'  Conipends. 

Stevenson's    PhotOSCOpy  Just  Ready 

Photoscgi'v.  (Skiascop)-  or  Retinoscopy)  By  Mark  D.  Stev- 
enson, M.  D.,  Ophthalmic  Surgeon  to  the  Akron  City  Hospital. 
i2mo  of  126  pages,  illustrated.  Cloth,  ;^i.25  net. 

Dr.  Stevenson's  work  fully  and  clearly  explains  the  use  of  this  objective  test  and  eluci- 
dates the  reasons  of  the  various  phenomena  observed.  The  illustrations  have  been  drawn 
with  special  attention  to  their  practical  usefulness. 


